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Blueprint Genetics Neuronal Migration Disorder Panel

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Neuronal Migration Disorder Panel Test code: MA2601 Is a 59 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of neuronal migration disorder. About Neuronal Migration Disorder Neuronal migration disorders (NMDs) are a group of birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. During development, neurons must migrate from the areas where they are originate to the areas where they will settle into their proper neural circuits. The structural abnormalities found in NMDs include schizencephaly, porencephaly, lissencephaly, agyria, macrogyria, polymicrogyria, pachygyria, microgyria, micropolygyria, neuronal heterotopias, agenesis of the corpus callosum, and agenesis of the cranial nerves. Mutations of many genes are involved in neuronal migration disorders, such as DCX in classical lissencephaly spectrum, TUBA1A in microlissencephaly with agenesis of the corpus callosum, and RELN and VLDLR in lissencephaly with cerebellar hypoplasia. Mutations in ARX cause a variety of phenotypes ranging from hydranencephaly or lissencephaly to early-onset epileptic encephalopathies, including Ohtahara syndrome and infantile spasms or intellectual disability with no brain malformations. Availability 4 weeks Gene Set Description Genes in the Neuronal Migration Disorder Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ACTB* Baraitser-Winter syndrome AD 55 60 ACTG1* Deafness, Baraitser-Winter syndrome AD 27 47 ADGRG1 Polymicrogyria, bilateral frontoparietal, Polymicrogyris, bilateral AR 27 35 perisylvian AKT3 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome AD 13 28 ARFGEF2 Heterotopia, periventricular AR 7 13 ARX Lissencephaly, Epileptic encephalopathy, Corpus callosum, agenesis of, XL 66 93 with abnormal genitalia, Partington syndrome, Proud syndrome, Hydranencephaly with abnormal genitalia, Mental retardation ATP6V0A2 Cutis laxa, Wrinkly skin syndrome AR 16 56 B3GALNT2 Muscular dystrophy-dystroglycanopathy AR 18 14 COL4A1 Schizencephaly, Anterior segment dysgenesis with cerebral involvement, AD 58 107 Retinal artery tortuosity, Porencephaly, Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, Brain small vessel disease COL4A2 Hemorrhage, intracerebral AD 14 12 DCX Lissencephaly, Subcortical laminal heterotopia XL 131 142 https://blueprintgenetics.com/ DYNC1H1 Spinal muscular atrophy, Charcot-Marie-Tooth disease, Mental AD 60 71 retardation EMX2 Schizencephaly AD 4 6 FAT4 Van Maldergem syndrome 2 AR 13 33 FH Hereditary leiomyomatosis and renal cell cancer AD/AR 178 207 FKTN Muscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy AD/AR 45 58 (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle) FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, XL 133 257 Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects FLVCR2 Proliferative vasculopathy and hydraencephaly-hydrocephaly syndrome AR 9 17 GMPPB Muscular dystrophy-dystroglycanopathy (congenital with brain and eye AR 19 41 anomalies), Limb-girdle muscular dystrophy-dystroglycanopathy GPSM2 Deafness, Chudley-McCullough syndrome AR 18 11 ISPD Muscular dystrophy-dystroglycanopathy AR 38 53 KATNB1 Lissencephaly 6, with microcephaly AR 6 10 KIF1BP Goldberg-Shprintzen megacolon syndrome AR 7 10 KIF7 Acrocallosal syndrome, Hydrolethalus syndrome, Al-Gazali-Bakalinova AR/Digenic 24 44 syndrome, Joubert syndrome L1CAM Mental retardation, aphasia, shuffling gait, and adducted thumbs XL 80 292 (MASA) syndrome, Hydrocephalus due to congenital stenosis of aqueduct of Sylvius, Spastic, CRASH syndrome, Corpus callosum, partial agenesis LAMA2 Muscular dystrophy, congenital merosin-deficient AR 199 301 LAMB1 Lissencephaly 5 AR 8 7 LAMC3 Cortical malformations, occipital AR 8 16 LARGE Muscular dystrophy-dystroglycanopathy AR 19 27 MACF1 Lissencephaly AD 1 9 MED12 Ohdo syndrome, Mental retardation, with Marfanoid habitus, FG XL 29 30 syndrome, Opitz-Kaveggia syndrome, Lujan-Fryns syndrome MEF2C Mental retardation AD 45 84 MPDZ Hydrocephalus, nonsyndromic, autosomal recessive 2 AR 14 24 NDE1 Microhydranencephaly, Lissencephaly AR 13 18 NSDHL Congenital hemidysplasia with ichthyosiform erythroderma and limb XL 15 28 defects (CHILD syndrome), CK syndrome OCLN*,# Pseudo-TORCH syndrome 1 (Band-like calcification with simplified AR 13 20 gyration and polymicrogyria) https://blueprintgenetics.com/ PAFAH1B1 Lissencephaly, Subcortical laminar heterotopia AD 121 169 PHGDH Neu-Laxova syndrome 1 AR 13 23 PIK3CA* Cowden syndrome, CLOVES AD 85 56 PIK3R2 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 AD 8 8 POMGNT2 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye AR 6 9 anomalies), type A, 8 POMT1 Muscular dystrophy-dystroglycanopathy AR 47 96 RAB18# Warburg micro syndrome 3 AR 5 5 RAB3GAP1 Warburg micro syndrome AR 29 66 RAB3GAP2# Warburg micro syndrome, Martsolf syndrome AR 11 15 RELN Lissencephaly, Epilepsy, familial temporal lobe AD/AR 25 44 RTTN Microcephaly, short stature, and polymicrogyria with or without seizures AR 16 16 SEPSECS Pontocerebellar hypoplasia, type 2D AR 10 15 SRPX2 Rolandic epilepsy, mental retardation, and speech dyspraxia XL 3 4 TMEM5 Muscular dystrophy-dystroglycanopathy AR 11 7 TUBA1A* Lissencephaly AD 69 65 TUBA8 Polymicrogyria with optic nerve hypoplasia AR 1 3 TUBB2A*,# Cortical dysplasia, complex, with other brain malformations 5 AD 12 5 TUBB2B*,# Polymicrogyria, asymmetric AD 21 30 TUBB3* Fibrosis of extraocular muscles, congenital, Cortical dysplasia, complex, AD/AR 28 25 with other brain malformations TUBG1* Cortical dysplasia, complex, with other brain malformations 4 AD 5 3 VLDLR Cerebellar ataxia, mental retardation, and dysequilibrium syndrome AR 11 24 WDR62 Microcephaly AR 33 48 YWHAE Distal 17p13.3 microdeletion syndrome, Endometrial stromal sarcoma, AD/AR 12 44 17p13.3 microduplication syndrome, Miller-Dieker syndrome *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 https://blueprintgenetics.com/ 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 ADGRG1 Chr16:57673285 c.-435_-421delCAACGGTTGCCAGGG NM_001145774.1 COL4A1 Chr13:110802675 c.*35C>A NM_001845.4 COL4A1 Chr13:110802678 c.*32G>A/T NM_001845.4 COL4A1 Chr13:110802679 c.*31G>T NM_001845.4 FKTN Chr9:108368857 c.648-1243G>T NM_006731.2 FLNA ChrX:153581587 c.6023-27_6023-16delTGACTGACAGCC NM_001110556.1 GMPPB Chr3:49761246 c.-87C>T NM_013334.3 rs780961444 L1CAM ChrX:153128846 c.3531-12G>A NM_000425.4 L1CAM ChrX:153131293 c.2432-19A>C NM_000425.4 L1CAM ChrX:153133652 c.1704-75G>T NM_000425.4 L1CAM ChrX:153133926 c.1547-14delC NM_000425.4 L1CAM ChrX:153136500 c.523+12C>T NM_000425.4 LAMA2 Chr6:129633984 c.3175-22G>A NM_000426.3 rs777129293 LAMA2 Chr6:129636608 c.3556-13T>A NM_000426.3 rs775278003 LAMA2 Chr6:129714172 c.5235-18G>A NM_000426.3 rs188365084 LAMA2 Chr6:129835506 c.8989-12C>G NM_000426.3 rs144860334 MEF2C Chr5:88179125 c.-510_-497delTCTTCCTCCTCCTC NM_002397.4 NSDHL ChrX:152037789 c.*129C>T NM_015922.2 rs145978994 POMT1 Chr9:134379574 c.-30-2A>G NM_007171.3 RTTN Chr18:67727297 c.4748-19T>A NM_173630.3 RTTN Chr18:67815044 c.2309+1093G>A NM_173630.3 TUBA8 Chr22:18604221 c.4-21_4-8delGTTGCTTCCCTCTC NM_018943.2 YWHAE Chr17:1303862 c.-458G>T NM_006761.4 Test Strengths The strengths of this test include: CAP accredited laboratory https://blueprintgenetics.com/ 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 Some of the panels include the whole mitochondrial genome (please see the Panel Content section) Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level Our publicly available analytic validation demonstrating complete details of test performance ~2,000 non-coding disease causing variants in our clinical grade NGS assay for panels (please see ‘Non-coding disease causing variants covered by this panel’ in the Panel Content section) Our rigorous variant classification scheme Our systematic clinical interpretation workflow using proprietary software enabling
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