Exome Sequencing in the Clinical Diagnosis of Sporadic Or Familial Cerebellar Ataxia

Supplementary Online Content

Fogel BL, Lee H, Deignan JL, et al. Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia. JAMA Neurol. Published online August 18, 2014. doi:10.1001/jamaneurol.2014.1944.

eTable 1. Cases With Pathogenic Variants Identified by Clinical Exome Sequencing (Complete Table) eTable 2. Cases With Variants of Uncertain Significance and/or Potential Pathogenicity Identified by Clinical Exome Sequencing (Complete Table) eTable 3. Cases With Nondiagnostic Results Following Exome Sequencing (Complete Table) eTable 4. Quality-Control Data for All Reported Next-Generation Exome Sequencing eTable 5. Missense or Nonsense HGMD Variants Causing Primary Cerebellar Ataxia Identified in the NHLBI Exome Variant Server Database eTable 6. Genes Identified by the Keyword Cerebellar Ataxia in OMIM and HGMD eAppendix. Clinical Evaluation for Acquired Causes of Cerebellar Ataxia eReferences

This supplementary material has been provided by the authors to give readers additional information about their work.

© 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 eTable 1. Cases With Pathogenic Variants Identified by Clinical Exome Sequencing (Complete Table)

Patient Sex Age Family History Ethnicity 1° Symptom Phenotype Multi-Exome Gene Inheritance Variant Transcript mRNA Protein MAF GERP SIFT PolyPhen2 Condel Segregation Disease Diagnosis ATX1 M 22 Sporadic Chinese Ataxia EO, HA, PN, POLR3A Recessive 1 10:79759834G>A ENST00000372371 c.2521G>A p.Gly841Ser 0.05% 4.62 Deleterious Poss Dam Deleterious Inherited OMIM 607694 Pathogenic 1 OLG, UMN, Classic WMA ATX6 M 45 Sporadic New Zealand Ataxia CA SYNE1 Recessive 6:152690632T>A ENST00000423061 c.9646A>T p.Lys3216* 0.00% N/A N/A N/A N/A Confirmed OMIM 610743Pathogenic 2 6:152754929C>A c.4482+1G>T p.? 0.00% N/A N/A N/A N/A Classic ATX9 M 51 Affected sister European Ataxia CA ANO10 Recessive 3:43647221insA ENST00000292246 c.123_124insA p.Asp45Argfs*9 0.00% N/A N/A N/A N/A Confirmed OMIM 613728 Pathogenic Homozygous Classic ATX18 F 49 Sporadic Hispanic Ataxia CA SYNE1 Recessive 6:152557375C>T ENST00000423061 c.20050C>T p.Arg6684* 0.00% N/A N/A N/A N/A Confirmed OMIM 610743 Pathogenic 6:152712499G>A c.7938G>A p.Trp2646* 0.00% N/A N/A N/A N/A Classic ATX26 F 9 Sporadic Lebanese Ataxia EO, PN Mother SLC52A2 Recessive 8:145584068G>A ENST00000329994 c.916G>A p.Gly306Arg 0.00% 4.54 Deleterious Prob Dam Deleterious Confirmed OMIM 607882 Pathogenic Father Homozygous Classic ATX29 M 16 Affected sister African Ataxia DEM, EO, Mother WFS1 Recessive 4:6293695G>A ENST00000226760 c.683G>A p.Arg228His 0.09% 3.54 Deleterious Prob Dam Deleterious HT Father OMIM 222300 Pathogenic HL, OA Father 4:6303017C>T c.1495C>T p.Leu499Phe 0.92% 3.07 Tolerated Benign Neutral HT Mother Variant 4:6303857G>A c.2335G>A p.Val779Met 0.84% 3.34 Tolerated Benign Neutral HT Mother 2 0.00% N/A N/A N/A N/A ND OMIM 610743 Pathogenic ATX35 F 57 Sporadic Palestinian Ataxia CA SYNE1 Recessive 6:152770776_152770786delinsG ENST00000423061 c.3417-10_3417delinsC P.? Homozygous Classic ATX43 M 50 Affected brother European Spasticity PN, WMA SPG7 Recessive 16:89613145C>T ENST00000268704 c.1529C>T p.Ala510Val 0.33% 3.39 Deleterious Prob Dam Deleterious ND OMIM 607259 Pathogenic 16:89620910delinsCCAAGTCTGTA c.2120_2121delTinsCCAAGTCTGTA p.Val707Alafs*38 0.00% N/A N/A N/A N/A Classic ATX48 F 16 Sporadic European Ataxia EO, HGH POLR3B Recessive 12:106821117T>C ENST00000228347 c.1244T>C p.Met415Thr 0.06% 4.50 Deleterious Benign Deleterious Confirmed OMIM 614381 Pathogenic 12:106895168G>A c.3052G>A p.Asp1018Asn 0.00% 4.62 Deleterious Prob Dam Deleterious Variant ATX58 M 13 Sporadic Iraqi Spasticity EO, OA, Mother NDUFS7 Recessive 19:1390954C>T ENST00000233627 c.313C>T p.Arg105Cys 0.00% 2.09 Deleterious Prob Dam Deleterious Confirmed OMIM 256000 Pathogenic PSY, WMA Father Homozygous Variant 2 0.00% 4.05 Deleterious Prob Dam Deleterious Confirmed OMIM 606002 Pathogenic ATX59 M 33 Sporadic Hispanic Ataxia EO, PN Mother SETX Recessive 9:135171259G>A c.6106G>A p.Gly2036Arg Father 9:135147145-135147147del c.7149_7151delinsAT p.Asp2383Glufs*26 0.00% N/A N/A N/A N/A Classic ATX60 M 26 Sporadic Iranian Ataxia EO, UMN SPG7 Recessive 16:89616967G>A ENST00000268704 c.1729G>A p.Gly577Ser 0.00% 2.87 Deleterious Prob Dam Deleterious ND OMIM 607259 Pathogenic Homozygous Classic ATX67 F 20 Sporadic European Ataxia EO, ID Mother ITPR1 Dominant 3:4687387G>T ENST00000357086 c.830G>T p.Ser277Ile 0.00% 4.62 Deleterious Prob Dam Deleterious De novo OMIM 117360 Pathogenic Father Classic ATX70 F 37 Affected brother Hispanic Ataxia EO, EP, MRE11A Recessive 11:94211948C>T ENST00000323929 c.497C>T p.Pro166Leu 0.00% 4.24 Deleterious Benign Neutral ND OMIM 604391 Pathogenic OMA 11:94219236G>T c.168G>T p.Leu56Phe 0.00% 2.13 Deleterious Prob Dam Deleterious Classic ATX72 M 16 Affected mother European Spasticity EO, PN Mother SPAST Dominant 2:32362033A>C ENST00000315285 c.1409A>C p.Asp470Ala 0.00% 4.62 Deleterious Prob Dam Deleterious Inherited OMIM 182601 Pathogenic Classic ATX76 M 62 Sporadic Ashkenazi Ataxia PN, WMA GBE1 Recessive 3:81691938A>C ENST00000429644 c.986A>C p.Tyr329Ser 0.00% 3.95 Deleterious Prob Dam Deleterious ND OMIM 263570 Pathogenic Homozygous Classic

© 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 eTable 2. Cases With Variants of Uncertain Significance and/or Potential Pathogenicity Identified by Clinical Exome Sequencing (Complete Table) Patient Sex Age Family History Ethnicity 1° Symptom Phenotype Multi-Exome Gene Inheritance Variant Transcript mRNA Protein MAF GERP SIFT PolyPhen2 Condel Segregation Disease Diagnosis ATX5 F 62 Sporadic Ashkenazi Ataxia PN WFS1 Recessive 4:6303194C>T ENST00000226760 c.1672C>T p.Arg558Cys 0.03% 3.14 Deleterious Prob Dam Deleterious ND OMIM 222300 VUS 1 Variant ATX8 F 20 Sporadic Hispanic Ataxia CA, EO SETX Recessive 9:135205028C>A ENST00000224140 c.1957C>A p.Gln653Lys 0.70% 3.21 Deleterious Prob Dam Deleterious Inherited OMIM 606002 VUS 2 9:135205178A>G c.1807A>G p.Asn603Asp 0.49% 4.13 Deleterious Benign Neutral Variant ATX10 F 22 Sporadic Hispanic Ataxia DEM, EO, GRID2 Recessive 4:94145790C>T ENST00000282020 c.989C>T p.Thr330Met 0.00% 3.72 Deleterious Poss Dam Deleterious Inherited OMIM no entry VUS 1 Asian WMA Variant ATX12 F 61 Affected twin sister European Spasticity GA ZFYVE26 Recessive 14:68236320G>A ENST00000347230 c.5612G>A p.Cys1871Tyr 0.89% -1.02 Tolerated Benign Neutral ND OMIM 270700 VUS 3 Ashkenazi 14:68265135C>T c.1844C>T p.Ser615Phe 0.92% 4.15 Deleterious Prob Dam Deleterious Variant ATX13 M 32 Sporadic Hispanic Ataxia ID AFG3L2 Dominant 18:12370848G>C ENST00000269143 c.292G>C p.Glu98Gln 0.00% 4.02 Tolerated Benign Neutral ND OMIM 610246 VUS Variant ATX17 F 29 Sporadic European Ataxia EO, PN SETX Recessive 9:135158661T>G ENST00000224140 c.6536T>G p.Ile2179Ser 0.00% 3.63 Deleterious Prob Dam Deleterious HT Mother OMIM 606002 VUS 9:135144798G>A ENST00000372169 c.7366G>A p.Ala2456Thr 0.00% -1.10 Deleterious Benign Neutral HZ Father Classic ATX21 F 47 Sporadic European Ataxia PN, UMN TGM6 Dominant 20:2377243A>G ENST00000202625 c.516A>G p.Ile172Met 0.00% 1.08 Deleterious Prob Dam Deleterious ND OMIM 613908 VUS Classic 1 ATX24 F 61 Sporadic Hispanic Ataxia CA GRID2 Recessive 4:93225859T>C ENST00000282020 c.52T>C p.Trp18Arg 0.02% 3.84 Deleterious Poss Dam Deleterious ND OMIM no entry VUS SPTBN2 Dominant 11:66472586C>A ENST00000533211 c.2161C>A p.Arg721Ser 0.00% 0.52 Deleterious Prob DamDeleterious OMIM 600224 WFS1 Recessive 4:6302580C>T ENST00000226760 c.1058C>T p.Ser353Phe 0.00% 3.00 Deleterious Prob Dam Deleterious OMIM 222300 Cla/Var/Cla/Var ATX27 F 29 Sporadic Asian Ataxia UMN SPTBN2 Dominant 11:66472288C>T ENST00000533211 c.2459C>T p.Thr820Met 0.00% 1.78 Deleterious Poss Dam Deleterious Inherited OMIM 600224 VUS Variant 1 ATX30 F 65 Sporadic European Ataxia CA CACNA1A Dominant 19:13470495C>G ENST00000360228 c.903C>G p.Phe301Leu 0.00% -2.55 Deleterious Prob Dam Deleterious ND OMIM 601011 VUS WFS1 Recessive 4:6303227-6303228GC>AG ENST00000226760 c.1705-1706GC>AG p.Ala569Ser 0.00% N/A Tolerated Benign Neutral OMIM 222300 Var/Var ATX32 F 81 Sporadic European Ataxia CA DYSF Recessive 2:71738977G>A ENST00000258104 c.383G>A p.Gly128Glu 0.30% 3.68 Deleterious Prob Dam Deleterious ND OMIM 253601 VUS 2:71838438C>G c.3967C>G p.Gln1323Glu 0.08% 4.47 Tolerated Benign Neutral WFS1 Recessive 4:6296783C>T ENST00000226760 c.728C>T p.Ala243Val 0.02% 2.78 Tolerated Poss Dam Neutral OMIM 222300 4:6302888C>T c.1366C>T p.Arg456Cys 0.0003% -3.86 Tolerated Prob Dam Deleterious Var/Var ATX34 M 54 Sporadic European Ataxia DEM, UMN, LRRK2 Dominant 12:40716220C>T ENST00000298910 c.5417C>T p.Thr1806Ile 0.00% 4.21 Tolerated Prob Dam Deleterious ND OMIM 607060 VUS Australian WMA Variant 1 ATX36 M 54 2 affected brothers Ashkenazi Ataxia EP, PSY, WFS1 Recessive 4:6302816C>G ENST00000226760 c.1294C>G p.Leu432Val 0.41% 2.90 Deleterious Prob Dam Deleterious ND OMIM 222300 VUS UMN Variant ATX37 F 10 Sporadic European Ataxia EO, PN WFS1 Recessive 4:6293706C>T ENST00000226760 c.694C>T p.Arg232Cys 0.00% 3.65 Tolerated Prob Dam Deleterious ND OMIM 222300 VUS 1 Hispanic Variant Asian ATX38 M 74 Affected son European Ataxia DEM, SZ SPG11 Recessive 15:44876420delAG ENST00000261866 c.5456_5457delAG p.Glu1819Alafs*10 0.00% N/A N/A N/A N/A ND OMIM 604360 VUS 1 Classic ATX39 M 72 Affected sibling, father European Parkinsonism EP, PN LRSAM1 Dominant 9:130265074T>C ENST00000323301 p.Cys690Arg 0.00% 4.08 Deleterious Benign Neutral ND OMIM 614436 VUS 1 DYSF Recessive 2:71797446C>T ENST00000410020 c.3067C>T p.Arg1023Trp 0.00% 2.70 Deleterious Prob Dam Deleterious OMIM 253601 Var/Var ATX46 M 44 Affected brother Hispanic Spasticity EO, EP, GA KIF1A Recessive 2:241659237G>A ENST00000320389 c.4672G>A p.Glu1558Lys 0.00% 2.61 Tolerated Benign Neutral ND OMIM 610357 VUS 1 Variant ATX52 M 58 Sporadic European Spasticity UMN PNPLA6 Recessive 19:7607741C>T ENST00000450331 c.1340C>T p.Pro447Leu 0.50% 2.96 Tolerated Benign Neutral ND OMIM 612020 VUS 19:7625546C>G c.3598C>G p.Gln1200Glu 0.01% 3.83 Tolerated Poss Dam Neutral Variant ATX54 F 52 Sporadic Hispanic Ataxia DEM TGM6 Dominant 20:2384143G>A ENST00000202625 c.1090G>A p.Glu364Lys 0.00% 2.49 Tolerated Benign Neutral HT Mother OMIM 613908 VUS PSEN1 Dominant 14:73678606A>C ENST00000324501 c.1085A>C p.Gln362Pro 0.00% 2.96 Tolerated Benign Neutral No paternal OMIM 600274 information Var/Var ATX55 F 51 Sporadic European Ataxia HA PDYN Dominant 20:1963652T>G ENST00000217305 c.79T>G p.Ser27Ala 0.00% 3.74 Tolerated Poss Dam Deleterious ND OMIM 610245 VUS Classic 1 ATX61 M 36 Affected father European Spasticity EO, WMA B4GALNT1 Recessive 12:58020552G>A ENST00000341156 c.1577G>A p.Arg526Gln 0.00% 2.86 Tolerated Prob Dam Deleterious ND OMIM 609195 VUS WFS1 Recessive 4:6303197G>A ENST00000226760 c.1675G>A p.Ala559Thr 0.39% 3.14 Tolerated Benign Neutral OMIM 222300 Cla/Var ATX62 M 70 Sporadic European Ataxia PN AMACR Recessive 5:33998931T>C ENST00000382085 c.554T>C p.Val185Ala 0.062% 4.31 Deleterious Poss Dam Deleterious ND OMIM 614307 VUS 1 Classic ATX63 M 2 Sporadic European Ataxia EO, Mother KLHL1 Recessive 13:70681591T>G ENST00000377844 c.241T>G p.Ser81Ala 0.00% 4.16 Tolerated Benign Neutral Non-maternal OMIM no entry VUS 1,4 Episodic SYNE1 Recessive 6:152469326G>C ENST00000423061 c.24617G>C p.Ser8206Thr 0.00% 5.01 Deleterious Prob Dam Deleterious No paternal OMIM 610743 6:152674425G>T c.11181G>T p.Met3727Ile 0.00% 4.47 Tolerated Benign Neutral information Unk/Var ATX64 M 71 Sporadic European Ataxia EP, PN EIF4G1 Dominant 3:184039843A>T ENST00000346169 c.1471A>T p.Ile491Phe 0.00% -0.52 Tolerated Benign Neutral ND OMIM 614251 VUS Variant ATX66 F 60 Multiple members European Ataxia DEM, PN, GBE1 Recessive 3:81640290T>G ENST00000429644 c.1134T>G p.Ser378Arg 0.16% 3.68 Tolerated Benign Neutral ND OMIM 263570 VUS diverse symptoms SZ 3:81810551C>A c.118C>A p.Pro40Thr 0.48% 3.20 Deleterious Benign Neutral Classic 1,5 ATX68 F 81 Sporadic European Ataxia PN PRX Recessive 19:40900066C>A ENST00000324001 c.4193C>A p.Ala1398Asp 0.00% 1.34 Deleterious Poss Dam Deleterious ND OMIM 605725 VUS C10ORF2 Recessive 10:102749087C>T ENST00000311916 c.1120C>T p.Arg374Trp 0.00% 4.54 Deleterious Prob Dam Deleterious OMIM 271245 Var/Var ATX69 M 68 Sporadic European Ataxia PN SYNE1 Recessive 6:152629741T>G ENST00000423061 c.17016T>G p.Tyr5672* 0.00% N/A N/A N/A N/A ND OMIM 610743 VUS 6:152771967T>C c.3209T>C p.Val1070Ala 0.37% 4.53 Tolerated Benign Neutral Variant 1 ATX73 F 61 Sporadic European Ataxia UMN SPG7 Recessive 16:89620213G>A ENST00000268704 c.1948G>A p.Asp650Asn 0.00% 3.57 Deleterious Prob Dam Deleterious ND OMIM 607259 VUS Classic ATX74 M 72 Sporadic European Ataxia PN TGM6 Dominant 20:2375121T>G ENST00000202625 c.31T>G p.Trp11Gly 0.02% 3.95 Deleterious Prob Dam Deleterious ND OMIM 613908 VUS Variant 1 ATX75 M 55 Affected mother European Ataxia PN SPG7 Recessive 16:89598369G>A ENST00000268704 c.1045G>A p.Gly349Ser 0.13% 4.50 Deleterious Prob Dam Deleterious ND OMIM 607259 VUS and 3 siblings WFS1 Recessive 4:6302886C>T ENST00000226760 c.1364C>T p.Thr455Met 0.02% 3.07 Tolerated Prob Dam Deleterious OMIM 222300 Var/Var

Patient Sex Age Family History Ethnicity 1° Symptom Phenotype Multi-Exome Diagnosis ATX2 M 54 Sporadic Japanese Ataxia CA Nondiagnostic ATX3 F 77 Sporadic European Ataxia PN Nondiagnostic ATX4 M 59 Sporadic Ashkenazi Ataxia UMN Nondiagnostic ATX7 F 24 Sporadic Hispanic Ataxia ID, PN, PSY, Nondiagnostic WMA ATX11 F 41 Affected brother Iranian Ataxia UMN Nondiagnostic ATX14 F 60 Sporadic Indian Ataxia WMA Nondiagnostic ATX15 M 40 Sporadic European Ataxia EP, PN Nondiagnostic Chinese ATX16 F 62 Sporadic European Ataxia UMN Nondiagnostic ATX19 F 35 Sporadic European Ataxia EO Nondiagnostic Japanese ATX20 F 46 Sporadic European Ataxia DEM, EP, Nondiagnostic UMN, WMA ATX22 M 69 Sporadic Ashkenazi Ataxia PN Nondiagnostic ATX23 F 39 Sporadic Hispanic Spasticity UMN Nondiagnostic ATX25 M 52 Sporadic Hispanic Spasticity UMN Nondiagnostic ATX28 F 61 Sporadic European Ataxia PSY Nondiagnostic ATX31 M 72 Sporadic Hispanic Ataxia PN Nondiagnostic ATX33 F 23 Sporadic European Ataxia EO Nondiagnostic ATX40 F 73 Multiple members European Ataxia EP, WMA Nondiagnostic diverse symptoms ATX41 F 69 Sporadic European Ataxia WMA Nondiagnostic ATX42 M 78 Sporadic European Ataxia CA Nondiagnostic ATX44 M 66 Affected sister European Ataxia PN Nondiagnostic ATX45 F 78 Affected brother Indian Ataxia DEM, EP, Nondiagnostic WMA ATX47 F 55 Sporadic European Spasticity PN Nondiagnostic ATX49 F 51 Sporadic Chinese Ataxia CA Nondiagnostic ATX50 F 65 2 affected sisters European Ataxia HA Nondiagnostic ATX51 F 70 Sporadic European Parkinsonism CA Nondiagnostic ATX53 F 73 Affected mother European Ataxia PN Nondiagnostic ATX56 M 14 Sporadic European Spasticity EO Mother Nondiagnostic Father ATX57 F 23 Sporadic European Ataxia EO, ID, PSY Mother Nondiagnostic Father ATX65 F 57 Affected mother, European Spasticity PN Mother Nondiagnostic daughter Sister ATX71 M 60 Sporadic European Spasticity PN, WMA Nondiagnostic

© 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 eTable 4. Quality-Control Data for All Reported Next-Generation Exome Sequencing Patient Total Uniquely Uniquely PCR RefSeq RefSeq Protein- Genomic Capture Total Passed Total Passed Allele Ti/Tv HT/HZ Ti/Tv HT/HZ Total Number of Sequence Aligned Aligned Duplicates Protein- Coding Ba se s Bases Specificity RefSeq SNVs in SNVs in Concordance Ratio of Ratio of Ratio of Ratio of Passed INDELs Reads Reads Reads (%) (%) Coding Covered at ≥ Ba se s/ Ge nom ic Ensembl dbSNP132 of Passed Known Known SNVs SNVs in Ensembl Bases 10X (%) Ba se s (%) Coding (%) SNVs in SNVs in SNVs in Absent in Absent in Coding Regions Regions dbSNP132 (%) dbSNP132 dbSNP132 dbSNP132 dbSNP132 ATX1 403556878 356559380 0.883541824 0.187106 5370292842 94.5 14301325861 0.375510138 20,590 95.9 99.9 3.1 1.2 2.6 19.9 1,112 ATX2 334780290 298148988 0.890581067 0.186401 4732789874 93.9 12033837201 0.39329017 21,048 96.4 99.9 3.1 1.2 2.9 15.3 1,038 ATX3 382616984 341137626 0.89159039 0.219219 4883135251 94.3 13207586557 0.369721995 20,788 96.8 99.9 3.2 1.5 2.7 18.6 1,125 ATX4 408406490 359897644 0.881224106 0.25058 5088130916 94.8 13369164524 0.380587052 21,360 96.6 99.8 3.1 1.5 2.8 20.5 1,145 ATX5 409609090 366078908 0.8937275 0.222958 5137242124 94.4 14109375326 0.364101316 21,352 96.3 99.9 3.2 1.5 2.7 26.2 1,156 ATX6 428097404 381685826 0.891586406 0.246029 5220759165 94.8 14269027099 0.365880528 20,915 97.1 99.9 3.2 1.4 2.6 17.0 1,114 ATX7 385806372 345141933 0.89459884 0.177164 5194137167 94.2 14088920610 0.368668212 21,319 96.6 99.9 3.1 1.5 3.2 21.2 1,150 ATX8 397457782 356446034 0.896814832 0.191482 5124973231 94.1 14305920140 0.358241426 22,642 96.1 99.9 3.1 1.8 2.7 33.6 1,112 ATX9 63160190 55034093 0.871341473 0.082707 1182535824 91.4 4878025423 0.242421005 19,922 97.3 99.9 3.1 1.4 2.6 31.7 1,226 ATX10 407094522 362852806 0.891323234 0.21073 5140874526 94.2 14218571139 0.361560559 20,942 95.5 99.9 3.1 1.2 2.8 19.4 1,102 ATX11 420761318 375526344 0.892492556 0.189885 5413869437 94.5 15105635256 0.358400646 20,797 96.2 99.9 3.2 1.4 2.6 14.6 1,132 ATX12 456650210 407339044 0.892015453 0.192945 6070825715 94.7 16295716722 0.372541191 20,973 96.3 99.8 3.1 1.4 2.6 30.0 1,129 ATX13 427202360 381571331 0.893186384 0.204014 5607864458 94.5 15071126600 0.372093249 20,552 97.1 99.8 3.2 1.4 2.6 15.3 1,119 ATX14 416796600 371414993 0.891118097 0.217131 5421466029 94.4 14435441210 0.375566354 20,940 95.6 99.9 3.2 1.4 2.7 24.2 1,078 ATX15 403384664 359294202 0.890698715 0.177467 5414933932 94.4 14661552364 0.369328827 23,024 96.0 99.9 3.2 1.9 2.7 22.7 1,157 ATX16 432373378 385756986 0.89218487 0.237097 5217216799 94.3 14581361002 0.3578004 20,852 96.9 99.8 3.2 1.4 3.1 19.4 1,161 ATX17 483485892 433223516 0.89604169 0.243665 5635851077 94.6 16241862068 0.346995379 20,825 97.1 99.9 3.2 1.5 3.4 28.5 1,236 ATX18 420696950 377232952 0.896685731 0.187837 5476995828 94.3 15211196649 0.360063442 21,082 96.4 99.9 3.2 1.4 2.7 21.3 1,179 ATX19 382547294 339317181 0.886994069 0.205343 4967239619 94.2 13357434235 0.37187079 21,440 96.9 99.9 3.1 1.5 3.0 17.1 1,186 ATX20 425914996 379831390 0.891800931 0.232824 5403706769 94.2 14471403965 0.373405841 20,785 96.7 99.9 3.2 1.5 2.4 23.4 1,139 ATX21 411477330 365333586 0.887858357 0.217577 5260985478 94.1 14135254749 0.37218894 20,659 97.1 99.8 3.2 1.5 2.9 20.4 1,122 ATX22 433031584 384131463 0.887074932 0.211673 5738771486 94.5 14975167372 0.383219188 20,663 97.0 99.9 3.1 1.4 2.5 14.1 1,138 ATX23 381448766 339083250 0.888935239 0.176456 5017029633 94.4 13870961653 0.361692993 21,364 96.7 99.8 3.2 1.5 3.0 23.8 1,152 ATX24 408387742 363232916 0.889431485 0.222461 5137646252 94.2 14027912029 0.366244545 20,716 95.2 100.0 3.1 1.2 2.5 19.8 1,131 ATX25 408025228 360043160 0.882404163 0.156955 5569360929 94.3 14979298513 0.371803855 20,839 97.0 99.9 3.2 1.5 3.1 20.1 1,108 ATX26 354615356 314298833 0.886309145 0.158019 4996024711 93.6 12820077663 0.389703155 21,534 96.1 99.9 3.2 1.4 2.9 19.2 1,177 ATX27 420368954 375121558 0.89236266 0.210605 5302945825 94.4 14696332761 0.360834632 21,430 95.8 99.9 3.1 1.2 2.7 19.5 1,216 ATX28 389258082 345244212 0.886928822 0.173179 5295290246 94.2 14167042395 0.373775281 20,799 96.8 99.8 3.2 1.4 2.6 20.1 1,172 ATX29 138774690 125054778 0.901135344 0.174222 4373744985 93.5 10155069589 0.430695718 24,897 95.2 99.9 3.2 1.8 2.6 13.7 1,396 ATX30 443198790 391505648 0.883363531 0.18927 5770615692 94.6 15715575167 0.367190868 20,879 97.0 99.9 3.1 1.5 2.7 19.6 1,132 ATX31 436623368 387037934 0.88643431 0.217527 5461405693 94.6 15003782162 0.364001932 20,720 95.6 99.9 3.1 1.2 2.9 19.0 1,190 ATX32 438148712 388428556 0.886522191 0.237671 5537110247 94.4 14690220245 0.376924931 20,636 97.3 99.9 3.2 1.5 2.4 19.3 1,181 ATX33 411036400 366545644 0.891759572 0.189457 5415156230 94.1 14736964296 0.367453983 20,650 97.3 99.9 3.2 1.5 2.8 26.4 1,177 ATX34 133530724 121505064 0.909940876 0.186622 4143071342 92.9 9701818875 0.427040681 20,900 97.1 99.9 3.2 1.4 2.3 14.1 1,456 ATX35 140112308 127836583 0.912386534 0.200351 4388138640 93.2 10026870675 0.437637901 21,125 96.1 99.9 3.1 1.4 2.7 20.6 1,456 ATX36 142470174 129147878 0.906490632 0.14457 4723516374 93.7 10820904992 0.436517683 21,234 96.5 99.8 3.2 1.4 2.8 15.5 1,490 ATX37 156407808 142847052 0.913298727 0.189496 5075313872 94.1 11372894391 0.446264047 21,757 96.8 99.9 3.2 1.7 2.7 17.0 1,524 ATX38 139711120 127121090 0.909885269 0.1809 4451811535 93.7 10218701527 0.435653348 20,909 97.0 99.9 3.2 1.5 2.5 14.3 1,408 ATX39 141555264 128537480 0.908037443 0.122516 4807574255 93.8 11056729210 0.434809803 20,927 97.1 99.9 3.2 1.4 2.5 23.2 1,453 ATX40 139897446 127135665 0.908777598 0.136355 4622244508 93.5 10731974906 0.430698408 20,861 97.1 99.9 3.1 1.5 2.4 30.0 1,281 ATX41 152183184 138103373 0.907481164 0.15513 4832342573 94.1 11392649406 0.424163195 20,916 97.0 99.8 3.2 1.5 2.7 19.2 1,317 ATX42 151126746 138186273 0.914373376 0.144219 4889842584 94.1 11628914620 0.420490024 21,080 97.2 99.9 3.2 1.5 2.6 27.4 1,289 ATX43 124669578 113344320 0.909157806 0.124395 4049439737 93.2 9766762916 0.414614317 20,928 97.2 99.8 3.1 1.5 2.6 14.7 1,283 ATX44 118641052 107690079 0.907696596 0.23082 3512304302 92.9 8155077022 0.430689286 21,012 97.1 99.9 3.1 1.5 3.0 13.6 1,426 ATX45 140894588 128597384 0.912720537 0.144922 4434764971 93.9 10834535461 0.4093175 21,554 96.2 99.9 3.1 1.5 2.7 16.2 1,522 ATX46 137478092 124972964 0.909039122 0.212903 4000897647 93.7 9680545671 0.413292575 21,669 96.1 99.9 3.1 1.5 2.7 16.8 1,564 ATX47 133479288 121567662 0.910760492 0.172304 4113288843 93.3 9879747339 0.416335429 21,071 97.2 99.9 3.1 1.5 2.3 19.0 1,291 ATX48 138407594 125833621 0.909152579 0.176981 4247524093 94.2 10191850238 0.416756918 20,627 97.1 99.9 3.1 1.4 2.2 22.8 1,190 ATX49 111471232 98078693 0.879856545 0.159091 3436411830 92.7 8102325542 0.424126606 20,591 95.9 99.9 3.2 1.2 3.1 25.4 1,208 ATX50 110891080 97708601 0.881122278 0.1627 3123020154 92.4 8029926860 0.388922615 20,906 97.4 99.8 3.1 1.5 2.6 24.2 1,276 ATX51 114829140 104590408 0.910835072 0.173042 3617564538 93.2 8501527362 0.425519367 20,593 97.1 99.9 3.1 1.4 2.6 22.4 1,208 ATX52 133061042 116974893 0.879106997 0.164777 4042800662 92.8 9599902362 0.421129352 20,727 96.8 99.9 3.1 1.4 2.5 16.8 1,236 ATX53 147445638 134418992 0.911651194 0.139222 4848839914 93.7 11346824677 0.427330117 20,967 96.3 99.9 3.2 1.4 2.8 23.4 1,427 ATX54 129075326 117685586 0.911758968 0.234318 3904311663 93 8883609335 0.439496101 21,407 96.3 99.9 3.1 1.5 2.8 30.9 1,351 ATX55 134980056 123134366 0.912241183 0.116641 4540215524 93.5 10708719296 0.423973717 21,048 97.2 99.9 3.1 1.4 2.4 17.0 1,347 ATX56 149994562 136644222 0.910994507 0.160551 4912786108 93.8 11272955493 0.435802848 21,029 97.1 99.9 3.2 1.5 2.4 13.4 1,439 ATX57 134391104 122754198 0.913410147 0.231972 3871670815 93.1 9264752916 0.417892506 20,735 97.2 99.8 3.1 1.5 2.5 17.2 1,373 ATX58 118367220 107208138 0.905724896 0.176148 3701871230 92.5 8641239209 0.428395875 21,051 96.3 99.8 3.2 1.4 3.0 12.6 1,369 ATX59 113768626 103497042 0.909715144 0.211182 3419887755 92.4 8074444603 0.423544643 20,967 97.0 99.9 3.1 1.6 2.8 18.9 1,401 ATX60 141342066 128173811 0.906834141 0.223318 3982650900 93.4 9798817799 0.406441979 21,246 96.0 99.8 3.1 1.4 2.8 14.8 1,399 ATX61 147161512 132530661 0.900579637 0.202485 3305971206 92.1 7800317804 0.423825194 21,210 97.1 99.8 3.1 1.5 2.7 10.6 1,336 ATX62 124817504 113241561 0.907257054 0.214055 3724237704 93 8761785367 0.42505466 20,352 97.4 99.9 3.2 1.4 3.2 12.9 1,389 ATX63 131253384 118894542 0.905839822 0.138864 4145179301 93.2 10073155097 0.411507543 20,967 97.2 99.9 3.1 1.5 2.7 20.3 1,350 ATX64 160715708 145455929 0.905051104 0.163058 4921728808 93.2 11776527149 0.417927012 20,739 97.3 99.8 3.1 1.4 2.8 19.0 1,301 ATX65 135729524 122769096 0.904512831 0.142324 4254757819 93.3 10347775571 0.411176082 21,154 97.0 99.9 3.1 1.5 2.6 13.1 1,717 ATX66 154088924 139710703 0.906688809 0.125297 5162049429 93.7 11973139009 0.431135847 21,163 96.4 99.9 3.1 1.4 2.8 13.1 1,695 ATX67 144206194 128295516 0.889667166 0.102207 4599146377 93.7 11268418161 0.408144809 20,770 97.0 99.9 3.1 1.5 2.5 27.4 1,323 ATX68 127973354 115917232 0.905791935 0.136996 4096170115 92.8 9849939856 0.415857373 20,863 97.1 99.9 3.1 1.5 2.7 33.4 1,305 ATX69 132225146 119198389 0.901480487 0.15761 4029980453 93.5 9859120186 0.408756601 21,556 97.0 99.9 3.1 1.5 2.3 12.4 1,547 ATX70 134423372 121307915 0.902431721 0.168592 4076389136 92.8 9911488067 0.411279226 21,854 96.3 99.9 3.2 1.5 2.9 24.8 1,528 ATX71 119305626 107728965 0.902966345 0.239417 3315444671 92.2 8063612020 0.411161234 20,870 97.3 99.9 3.2 1.4 2.9 14.2 1,357 ATX72 151381462 136090068 0.898987671 0.194354 4510396909 93.1 10762156600 0.41909787 20,700 97.4 99.9 3.1 1.4 2.6 15.3 1,314 ATX73 150675466 136593490 0.906541016 0.181416 4644026827 93.3 10979389304 0.422976788 21,196 97.2 99.9 3.1 1.5 2.5 18.3 1,468 ATX74 138268474 124711036 0.901948451 0.217481 4107512051 92.8 9587957522 0.428403238 21,443 96.6 99.9 3.1 1.4 2.6 14.9 1,439 ATX75 116028034 104598568 0.901493927 0.308777 3015932215 91.7 7116411363 0.42379959 20,613 97.2 99.9 3.2 1.4 2.7 14.1 1,373 ATX76 129268794 117168037 0.906390733 0.2035 3707308084 92.4 9158263655 0.40480469 20,886 96.7 99.9 3.2 1.4 2.7 19.6 1,407 ATX26- 372102634 329471180 0.885430927 0.180431 5218666333 94.1 13411711570 0.389112628 21,714 96.0 99.9 3.1 1.4 2.7 14.6 1,160 Father ATX26- 383631908 339849264 0.885873299 0.182247 5293513542 94.1 13799015826 0.383615296 21,619 96.3 99.9 3.1 1.5 2.9 16.4 1,217 Mother ATX29- 118996614 107316025 0.901840997 0.134878 3981775651 92.7 9136258179 0.435821271 24,310 95.6 99.9 3.2 1.9 2.7 16.5 1,369 Father ATX29- 125668846 113684608 0.904636365 0.185683 3933162732 93.2 9110021882 0.431740207 25,192 95.1 99.9 3.2 1.8 2.8 23.1 1,435 Mother ATX56- 149005052 135677820 0.910558523 0.276924 4111028682 93.2 9649433181 0.426038359 20,931 97.0 99.9 3.1 1.4 2.6 14.1 1,400 Father ATX56- 138674276 126364372 0.911231525 0.195259 4340510221 93.6 9997505831 0.434159309 21,082 97.1 99.9 3.2 1.5 2.7 29.6 1,414 Mother ATX57- 157819386 143885989 0.91171302 0.232722 4639408745 93.6 10856318892 0.427346395 20,887 97.2 99.8 3.1 1.5 2.5 20.1 1,388 Father ATX57- 146486144 133633299 0.912258971 0.19767 4507713338 93.4 10539713174 0.427688426 20,719 97.1 99.9 3.2 1.5 2.6 16.3 1,350 Mother ATX58- 219017566 198299422 0.90540419 0.259376 6102294924 94.8 14352691674 0.425167283 21,403 96.2 99.8 3.2 1.5 2.9 17.3 1,452 Father ATX58- 116265506 105540920 0.9077578 0.280989 3189115283 92 7441140824 0.42857881 21,086 96.0 99.9 3.2 1.5 2.6 38.4 1,368 Mother ATX59- 106377976 96915188 0.91104561 0.229168 3173990464 92.1 7389457334 0.429529574 20,846 96.4 99.9 3.1 1.4 2.7 12.3 1,411 Father ATX59- 113498772 103410197 0.911112915 0.184482 3627098094 92.5 8338559359 0.434978986 20,673 97.3 99.8 3.1 1.5 2.8 20.6 1,352 Mother ATX63- 121683618 110710189 0.909819997 0.129016 3949434811 92.9 9500885489 0.415691234 20,880 96.8 99.9 3.1 1.5 2.5 24.5 1,346 Mother ATX65- 140430756 126868058 0.903420744 0.129144 4474575099 93.6 10852346856 0.412314051 21,420 96.9 99.9 3.1 1.5 2.7 12.0 1,745 Mother ATX65- 125642162 114108431 0.908201747 0.167884 3894941183 93.3 9336306864 0.417182216 21,278 97.0 99.9 3.2 1.5 2.6 23.8 1,643 Sister ATX67- 146045888 129808822 0.888822163 0.081446 4947288636 93.7 11662729737 0.424196457 20,837 96.8 99.9 3.2 1.5 2.5 16.0 1,367 Father ATX67- 142137972 127077569 0.894043775 0.108151 4541698375 93.6 11095819098 0.409316188 20,726 97.1 99.9 3.1 1.4 2.6 25.1 1,306 Mother ATX72- 136516476 123341897 0.903494586 0.26174 3775275380 92.4 8960863324 0.421307104 20,684 97.3 99.9 3.2 1.5 2.8 22.8 1,316 Mother

© 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 eTable 5. Missense or Nonsense HGMD Variants Causing Primary Cerebellar Ataxia Identified in the NHLBI Exome Variant Server Database

Gene Known Mutations in HGMD Known Mutations in HGMD Observed in EVS (total) Known Mutation in HGMD Observed in EVS Most Commonly (single variant) MAF (Most Common Variant, %) ABCB7 4 0 ‐ ‐ ABHD12 2 0 ‐ ‐ ADCK3 14 5 NM_020247.4:c.1286A>G | NP_064632.2:p.Y429C 0.04% AFG3L2 13 0 ‐ ‐ ANO10 2 0 ‐ ‐ APTX 18 2 NM_175073.2:c.596G>A | NP_778243.1:p.R199H 0.62% ATCAY 1 0 ‐ ‐ ATM 198 15 NM_000051.3:c.5071A>C | NP_000042.3:p.S1691R 0.22% ATP2B3 1 0 ‐ ‐ ATP8A2 1 0 ‐ ‐ C10orf2 5 0 ‐ ‐ CA8 3 0 ‐ ‐ CACNA1A 56 4 NM_001127221.1:c.1360G>A | NP_001120693.1:p.A454T 0.42% COX20 1 0 ‐ ‐ DARS2 1 0 ‐ ‐ DNMT1 4 0 ‐ ‐ EEF2 1 0 ‐ ‐ FGF14 1 0 ‐ ‐ FLVCR1 4 1 NM_014053.3:c.361A>G | NP_054772.1:p.N121D 0.01% FXN 23 1 NM_000144.4:c.389G>T | NP_000135.2:p.G130V 0.01% GBA2 4 0 ‐ ‐ GJB1 1 0 ‐ ‐ GOSR2 1 0 ‐ ‐ ITPR1 3 0 ‐ ‐ KCNA1 25 0 ‐ ‐ KCNC3 3 0 ‐ ‐ KCND3 6 0 ‐ ‐ KCNJ10 6 0 ‐ ‐ KCTD7 1 0 ‐ ‐ MECP2 1 0 ‐ ‐ MRE11A 6 0 ‐ ‐ MTPAP 1 0 ‐ ‐ OPA1 4 0 ‐ ‐ OPA3 1 0 ‐ ‐ OTUD4 1 1 NM_001102653.1:c.998G>T | NP_001096123.1:p.G333V 0.02% PDYN 5 1 NM_024411.4:c.414G>T | NP_077722.1:p.R138S 0.01% PEX10 2 0 ‐ ‐ PIK3R5 1 1 NM_001142633.2:c.1885C>T | NP_001136105.1:p.P629S 0.91% PNPLA6 1 0 ‐ ‐ POLG 6 2 NM_002693.2:c.2207A>G | NP_002684.1:p.N736S 0.05% POLR3A 2 1 NM_007055.3:c.2015G>A | NP_008986.2:p.G672E 0.01% PRICKLE1 1 1 NM_153026.2:c.311G>A | NP_694571.2:p.R104Q 0.01% PRKCG 27 1 NM_002739.3:c.2075T>G | NP_002730.1:p.V692G 0.02% RNF170 1 0 ‐ ‐ RNF216 5 0 ‐ ‐ SACS 91 6 NM_014363.4:c.8393C>A | NP_055178.3:p.P2798Q 0.29% SCN2A 1 0 ‐ ‐ SDHA 1 0 ‐ ‐ SETX 54 3 NM_015046.5:c.6792A>G | NP_055861.3:p.I2264M 0.02% SLC1A3 2 0 ‐ ‐ SPTBN2 3 0 ‐ ‐ SRD5A3 1 0 ‐ ‐ STUB1 6 0 ‐ ‐ SYNE1 8 0 ‐ ‐ SYT14 1 0 ‐ ‐ TDP1 1 0 ‐ ‐ TGM6 3 0 ‐ ‐ TPP1 1 0 ‐ ‐ TTC19 1 0 ‐ ‐ TTPA 10 1 NM_000370.3:c.358G>A | NP_000361.1:p.A120T 0.01% VLDLR 1 0 ‐ ‐ WWOX 1 0 ‐ ‐

Genes identified by the keyword "cerebellar ataxia" in OMIM and HGMD ABCB7

ADCK3 AFG3L2 AHI1

AMACR

ANO10 AP4M1 APOA1 APOB APTX ARSA ARSG

ATCAY ATM ATN1 ATP13A2 ATP1A2

ATP2B3

ATP8A2 ATXN1 ATXN10 ATXN2 ATXN3 ATXN7 ATXN8 ATXN8OS AUH BEAN1 C9orf72

CA8

CACNA1A CAMTA1 CC2D2A CLAM CLCN2 CLN6 CLPP COA5 COG8 COL18A1 COL7A1 COQ2 COX10 COX14 COX20 COX6B1 CP CSE CSPP1 CSTB CTSA CYP27A1 CYP7B1 DARS2 DFNB81 DKC1 DNAJC19 DNAJC5

DNMT1 DPM1 DPYD DPYSL5 EEF2 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2B5 ELP4 ERCC2 ERCC3 ERCC4 ERDA1 FASTKD2 FCMTE1 FCMTE2 FGF14 FLVCR1 FMR1 FOXRED1 FTL FXN GAN

GBA2 GBX2 GFAP GJC2

GRID2

GRM1 GRN GTF2H5 HEXB HOXD13 HSD17B4 HTT IFT140 ITM2B ITPR1 KAL1 KCNC3 KCND3 KCNMA1 KIAA0226 KIF1A KIF1C KIF21A LMNB1 LYST MAN2B1 MARS2 MCM3AP MLC1

MLLT3 MMP1 MRE11A MTPAP MVK MYO7A NBN NDUFA1 NDUFA11 NDUFAF1 NDUFAF2 NDUFAF3 NDUFAF4 NDUFAF5 NDUFB3 NDUFB9 NDUFS1 NDUFS2 NDUFS3 NDUFS4 NDUFS6 NDUFV1 NDUFV2 NEU1 NOL3 NOP56 NOTCH3 NPC1 NPC2

NUBPL NUP62 OFD1

OPA3 OTUD4 OTX2 PAX6 PDHA1

PDYN PET100

PEX2 PEX7 PHYH PLA2G1B PLA2G6

PLEKHG4 PLP1 PMM2 PNPLA6

POLG POLR3B PPP2R2B PPT1 PRICKLE1 PRKCG PRNP PRPS1 PSEN1 PTEN QKI RBPMS RNF216 RORA RPGRIP1L

SACS SCA20 SCA21 SCA25 SCA30 SCA32 SCA34 SCAR2 SCAR6 SCASI SCN8A

SETX SIL1 SLC17A5 SLC19A3 SLC20A2 SLC25A15 SLC2A1 SLC39A4 SLC5A2 SLC6A19 SMAD4 SOX10 SPG16 SPTBN2

SRD5A3

STUB1

SYNE1 SYT14 TACO1 TARDBP TBP TDP1 TGM6 TINF2 TMEM67 TPP1 TTBK2 TTC19 TTR UCHL1

VLDLR WDR81 WFS1

WWOX ZFYVE26 ZNF592

Basic Clinical/Diagnostic Evaluation (All Patients) Clinical Examination by a Neurologist (Ataxia Specialist) Complete Detailed Family History MRI of the Brain

Basic Laboratory Evaluation (All Patients) Antinuclear antibodies Complete blood count including platelets and differential Copper Erythrocyte sedimentation rate Folate Hemoglobin A1C Homocysteine Lactate Metabolic panel including serum electrolytes, renal function, liver function, and random glucose Methylmalonic acid Pyruvate Rapid plasma reagin (RPR) test Vitamin B12 Vitamin E Thyroid stimulating hormone

Advanced Laboratory Evaluation (Based on Phenotype/Clinical Presentation) Acylcarnitine profile Ammonia Angiotensin converting enzyme Celiac autoantibodies (e.g., endomysial, tissue-transglutaminase, others) Cerebellar autoantibodies (e.g., Yo, Hu, Ri, and others) Cerebrospinal fluid analysis (e.g., cell count, glucose, protein, and various other studies) Ceruloplasmin Creatine kinase GAD65 autoantibodies Gliadin autoantibodies Human Immunodeficiency Virus (HIV) screening Human T-Cell Lymphotropic Virus (HTLV) screening Ketones Lipids (fasting) Lyme Disease screening Lysosomal enzymes

© 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 Plasma amino acids Serum immunofixation Serum protein electrophoresis Sjögren syndrome (SSA/SSB) autoantibodies Thyroid autoantibodies (e.g., thyroglobulin, thyroid peroxidase, etc.) Urine heavy metals Urine organic acids Urine protein electrophoresis Very long chain fatty acids

Additional Diagnostic Testing (As Indicated) Autonomic testing Brainstem auditory evoked responses Computed tomography of chest/abdomen/pelvis Conjunctival or skin biopsy Diffusion tensor imaging of the brain Electroencephalogram Electromyogram Electronystagmogram Magnetic resonance angiography of the head/neck Magnetic resonance imaging of the cervical-, thoracic-, and/or lumbar-spine Magnetic resonance spectroscopy Muscle biopsy Nerve conduction studies Positron emission tomography of brain and/or body Polysomnogram Somatosensory evoked potentials Visual evoked potentials

eReferences 1. Fogel BL, Perlman S. An approach to the patient with late-onset cerebellar ataxia. Nat Clin Pract Neurol. Nov 2006;2(11):629-635; quiz 621 p following 635. 2. Fogel BL, Perlman S. Cerebellar disorders: Balancing the approach to cerebellar ataxia. In: Gálvez-Jiménez N, Tuite PJ, eds. Uncommon Causes of Movement Disorders. 1st ed. Cambridge, NY: Cambridge University Press; 2011:198-216. 3. Shakkottai VG, Fogel BL. Clinical neurogenetics: autosomal dominant spinocerebellar ataxia. Neurol Clin. Nov 2013;31(4):987-1007. 4. Fogel BL, Vickrey BG, Walton-Wetzel J, Lieber E, Browner CH. Utilization of genetic testing prior to subspecialist referral for cerebellar ataxia. Genet Test Mol Biomarkers. Aug 2013;17(8):588-594.