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Blueprint Genetics Optic Atrophy Panel

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Blueprint Genetics Optic Atrophy Panel Optic Atrophy Panel Test code: OP0301 Is a 68 gene panel that includes assessment of non-coding variants. In addition, it also includes the maternally inherited mitochondrial genome. This is ideal for patients with a clinical suspicion or diagnosis of isolated or syndromic optic atrophy. About Optic Atrophy Optic atrophy is a condition that affects the optic nerve, which carries impulses from the eye to the brain. Optic atrophy type 1 (OA1) is clinically characterized by progressive decrease in visual acuity from early childhood onwards. Clinical presentation can be highly variable. The visual impairment is usually moderate, but ranges from severe (legal blindness with acuity <1/20) to mild, accompanied by visual field and color vision defects. OA1 is characterized by the preferential loss of retinal ganglion cells and is inherited in an autosomal dominant manner. Approximately 80% of the familial and 50% of the sporadic cases with OA1 are explained by variants in OPA1, which encodes a mitochondrial inner membrane protein. Optic atrophy can also be syndromic. For example, deafness-dystonia-optic neuronopathy (DDON) syndrome (Mohr-Tranebjaerg syndrome) is inherited in an X-linked manner and caused by variants in TIMM8A. Biallelic variants in WFS1 are associated with optic atrophy as part of the autosomal recessive Wolfram syndrome. Autosomal dominant Charcot-Marie-Tooth hereditary neuropathy type 2A is caused by variants in MFN2. Variants in C12ORF65 are implicated in autosomal recessive hereditary spastic paraplegias. Availability 4 weeks Gene Set Description Genes in the Optic Atrophy Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ACO2 Optic atrophy, Infantile cerebellar-retinal degeneration AR 16 15 AFG3L2* Spastic ataxia, Spinocerebellar ataxia AD/AR 22 40 ATAD3A* Harel-Yoon syndrome AD/AR 4 17 AUH 3-methylglutaconic aciduria AR 12 11 C12ORF65 Spastic paraplegia, Combined oxidative phosphorylation deficiency AR 10 11 C19ORF12 Spastic Paraplegia, Neurodegeneration with brain iron accumulation AR 15 37 CISD2* Wolfram syndrome 2 AR 2 4 DNAJC19 3-methylglutaconic aciduria AR 3 6 DNM1L Encephalopathy due to defective mitochondrial and peroxisomal fission AD 17 20 1 FDXR Auditory neuropathy and optic atrophy AR 5 19 MECR Dystonia, childhood-onset, with optic atrophy and basal ganglia AR 7 6 abnormalities (DYTOABG) https://blueprintgenetics.com/ MFN2 Hereditary motor and sensory neuropathy, Charcot-Marie-Tooth AD/AR 70 223 disease MT-ATP6 Neuropathy, ataxia, and retinitis pigmentosa, Leber hereditary optic Mitochondrial 19 neuropathy, Ataxia and polyneuropathy, adult-onset, Cardiomyopathy, infantile hypertrophic, Leigh syndrome, Striatonigral degeneration, infantile, mitochondrial MT-ATP8 Cardiomyopathy, apical hypertrophic, and neuropathy, Mitochondrial 4 Cardiomyopathy, infantile hypertrophic MT-CO1 Myoglobinuria, recurrent, Leber hereditary optic neuropathy, Mitochondrial 17 Sideroblastic anemia, Cytochrome C oxidase deficiency MT-CO2 Cytochrome c oxidase deficiency Mitochondrial 8 MT-CO3 Cytochrome c oxidase deficiency, Leber hereditary optic neuropathy Mitochondrial 9 MT-CYB Mitochondrial 69 MT-ND1 Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke- Mitochondrial 21 like episodes, Leber hereditary optic neuropathy, Leber optic atrophy and dystonia MT-ND2 Leber hereditary optic neuropathy, Mitochondrial complex I deficiency Mitochondrial 6 MT-ND3 Leber optic atrophy and dystonia, Mitochondrial complex I deficiency Mitochondrial 7 MT-ND4 Leber hereditary optic neuropathy, Leber optic atrophy and dystonia, Mitochondrial 11 Mitochondrial complex I deficiency MT-ND4L Leber hereditary optic neuropathy Mitochondrial 2 MT-ND5 Myoclonic epilepsy with ragged red fibers, Mitochondrial myopathy, Mitochondrial 19 encephalopathy, lactic acidosis, and stroke-like episodes, Leber hereditary optic neuropathy, Mitochondrial complex I deficiency MT-ND6 Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke- Mitochondrial 16 like episodes, Oncocytoma, Leber hereditary optic neuropathy, Leber optic atrophy and dystonia, Mitochondrial complex I deficiency MT-RNR1 Deafness, mitochondrial Mitochondrial 3 MT-RNR2 Chloramphenicol toxicity/resistance Mitochondrial 2 MT-TA Mitochondrial 4 MT-TC Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke- Mitochondrial 3 like episodes MT-TD Mitochondrial 1 MT-TE Diabetes-deafness syndrome, Mitochondrial myopathy, infantile, Mitochondrial 5 transient, Mitochondrial myopathy with diabetes MT-TF Myoclonic epilepsy with ragged red fibers, Nephropathy, Mitochondrial 7 tubulointerstitial, Encephalopathy, mitochondrial, Epilepsy, mitochondrial, Myopathy, mitochondrial, Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes MT-TG Mitochondrial 3 https://blueprintgenetics.com/ MT-TH Mitochondrial 4 MT-TI Mitochondrial 7 MT-TK Mitochondrial 5 MT-TL1 Cytochrome c oxidase deficiency, Myoclonic epilepsy with ragged red Mitochondrial 14 fibers, Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Diabetes-deafness syndrome, Cyclic vomiting syndrome, SIDS, susceptibility to MT-TL2 Mitochondrial multisystemic disorder, Progressive external Mitochondrial 5 ophthalmoplegia MT-TM Leigh syndrome, Mitochondrial multisystemic disorder Mitochondrial 1 MT-TN Progressive external ophthalmoplegia, Mitochondrial multisystemic Mitochondrial 3 disorder MT-TP Mitochondrial 2 MT-TQ Mitochondrial multisystemic disorder Mitochondrial 2 MT-TR Encephalopathy, mitochondrial Mitochondrial 2 MT-TS1 Myoclonic epilepsy with ragged red fibers, Mitochondrial myopathy, Mitochondrial 10 encephalopathy, lactic acidosis, and stroke-like episodes MT-TS2 Mitochondrial multisystemic disorder Mitochondrial 2 MT-TT Mitochondrial 5 MT-TV Hypertrophic cardiomyopathy (HCM), Leigh syndrome, Mitochondrial Mitochondrial 3 multisystemic disorder MT-TW Leigh syndrome, Myopathy, mitochondrial Mitochondrial 8 MT-TY Mitochondrial multisystemic disorder Mitochondrial 4 MTPAP Spastic ataxia AR 1 2 NDUFS1 Mitochondrial complex I deficiency AR 22 28 NR2F1 Bosch-Boonstra optic atrophy syndrome AD 23 34 OPA1 Optic atrophy, Optic atrophy 1, Optic atrophy with or without deafness, AD/AR 96 390 Ophthalmoplegia, myopathy, ataxia, and neuropathy, Behr synrome, Mitochondrial DNA depletion syndrome 14 OPA3 Optic atrophy, 3-methylglutaconic aciduria AD/AR 13 15 POLG POLG-related ataxia neuropathy spectrum disorders, Sensory ataxia, AD/AR 89 290 dysarthria, and ophthalmoparesis, Alpers syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndrome PRPS1* Phosphoribosylpyrophosphate synthetase I superactivity, Arts XL 27 32 syndrome, Charcot-Marie-Tooth disease, X-linked recessive, 5, Deafness, X-linked 1 https://blueprintgenetics.com/ RTN4IP1 Optic atrophy 10 with or without ataxia, mental retardation, and AR 2 12 seizures SLC25A46 Neuropathy, hereditary motor and sensory, type VIB AR 14 17 SLC52A2 Brown-Vialetto-Van Laere syndrome AR 27 25 SNX10 Osteopetrosis, autosomal recessive 8 AR 3 13 SPG7 Spastic paraplegia AR 69 111 TIMM8A* Mohr-Tranebjaerg syndrome, Jensen syndrome, Opticoacoustic nerve XL 11 21 atrophy with dementia TMEM126A Optic atrophy AR 3 1 TSFM Combined oxidative phosphorylation deficiency AR 6 6 UCHL1 Parkinson disease 5, autosomal dominant, Spastic paraplegia 79, AD/AR 5 5 autosomal recessive WFS1 Wolfram syndrome, Deafness, Wolfram-like syndrome, autosomal AD/AR 69 362 dominant, Deafness, autosomal dominant 6/14/38, Cataract 41 YME1L1 Optic atrophy 11 1 1 ZNHIT3 PEHO syndrome 5 1 *Some regions of the gene are duplicated in the genome. Read more. # The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads), and/or the gene has exons listed under Test limitations section that are not included in the panel as they are not sufficiently covered with high quality sequence reads. The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#). Due to possible limitations these genes may not be available as single gene tests. Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), mitochondrial (mi), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD). The list of associated, gene specific phenotypes are generated from CGD or Mitomap databases. Non-coding disease causing variants covered by the panel Gene Genomic location HG19 HGVS RefSeq RS-number OPA1 Chr3:193334932 c.449-34dupA NM_130837.2 OPA1 Chr3:193374829 c.2179-40G>C NM_130837.2 SLC52A2 Chr8:145582843 c.-110-1G>A NM_024531.4 TIMM8A ChrX:100601671 c.133-23A>C NM_004085.3 rs869320666 WFS1 Chr4:6271704 c.-43G>T NM_006005.3 https://blueprintgenetics.com/ Test Strengths The strengths of this test include: CAP accredited laboratory CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance Careful construction of clinically effective and scientifically justified gene panels
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