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Blueprint Genetics X-Linked Intellectual Disability Panel

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X-linked Intellectual Disability Panel Test code: NE0601 Is a 106 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of X-linked intellectual disability. Please note, this panel does not include FMR1 trinucleotide repeat expansion and is not ideal for patients suspected to have Fragile X syndrome. About X-linked Intellectual Disability Intellectual disability (ID) is more common in males than females in the general population, presumed to be due to mutations in genes on the X chromosome. X-linked ID accounts for approximately 16% of males with intellectual disability. In addition to karyotype abnormalities and Fragile X syndrome, numerous X-linked genes exist where mutations have been described that result in either syndromic or non‐syndromic ID. Epileptic seizures accompany ID in almost half of these X-linked disorders.This panel allows for systematic screening of X-linked nonsyndromic and syndromic intellectual disability. Availability 4 weeks Gene Set Description Genes in the X-linked Intellectual Disability Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ABCD1* Adrenoleukodystrophy XL 95 663 ACSL4 Mental retardation XL 6 7 AFF2 Premature ovarian failure, Mental retardation, X-linked, FRAXE type XL 6 25 AP1S2* Mental retardation, syndromic, Fried (Pettigrew syndrome) XL 11 12 ARHGEF6 Mental retardation XL 2 5 ARHGEF9 Epileptic encephalopathy, early infantile XL 10 23 ARX Lissencephaly, Epileptic encephalopathy, Corpus callosum, agenesis of, XL 66 93 with abnormal genitalia, Partington syndrome, Proud syndrome, Hydranencephaly with abnormal genitalia, Mental retardation ATP6AP2 Mental retardation, syndromic, Hedera, Parkinsonism with spasticity XL 3 6 ATP7A Menkes disease, Occipital horn syndrome, Spinal muscular atrophy, distal, XL 116 354 X-linked 3 ATRX Carpenter-Waziri syndrome, Alpha-thalassemia/mental retardation XL 65 165 syndrome, Holmes-Gang syndrome, Juberg-Marsidi syndrome, Smith- Fineman-Myers syndrome, Mental retardation-hypotonic facies syndrome BCOR Microphthalmia, syndromic, Oculofaciocardiodental syndrome XL 40 53 BRWD3 Mental retardation XL 9 17 https://blueprintgenetics.com/ CASK Mental retardation and microcephaly with pontine and cerebellar XL 87 112 hypoplasia, FG syndrome, Mental retardation CDKL5 Epileptic encephalopathy, early infantile, Rett syndrome, atypical, XL 312 331 Angelman-like syndrome CLCN4 Mental retardation, X-linked 49 XL 21 17 CNKSR2 Epileptic encephalopathy, X-linked mental retardation, Epilepsy and X- XL 7 6 linked mental retardation CUL4B Mental retardation, syndromic, Cabezas XL 23 38 DCX Lissencephaly, Subcortical laminal heterotopia XL 131 142 DDX3X Mental retardation, X-linked 102 XL 84 51 DKC1 Hoyeraal-Hreidarsson syndrome, Dyskeratosis congenita XL 48 74 DLG3 Mental retardation XL 11 17 ELK1* Intellectual disability XL 3 FANCB Fanconi anemia XL 11 21 FGD1 Aarskog-Scott syndrome, Mental retardation, syndromic XL 29 51 FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, XL 133 257 Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects FMR1 Premature ovarian failure, Fragile X syndrome, Fragile X tremor/ataxia XL 13 76 syndrome FRMPD4 Mental retardation, X-linked 104 4 6 FTSJ1 Mental retardation XL 5 10 GDI1 Mental retardation XL 7 11 GK* Glycerol kinase deficiency XL 11 35 GPC3 Simpson-Golabi-Behmel syndrome XL 33 75 GRIA3 Mental retardation XL 12 23 HCCS Linear skin defects with multiple congenital anomalies 1 (MIDAS XL 7 13 syndrome) HDAC8 Cornelia de Lange syndrome XL 41 50 HPRT1 Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome XL 72 427 HSD17B10 17-beta-hydroxysteroid dehydrogenase X deficiency, Mental retardation, XL 10 15 syndromic HUWE1 Mental retardation, syndromic, Turner XL 37 54 IDS* Mucopolysaccharidosis XL 85 637 https://blueprintgenetics.com/ IGBP1 Corpus callosum, agenesis of, with mental retardation, ocular coloboma XL 1 2 and micrognathia IL1RAPL1 Mental retardation XL 17 41 IQSEC2 Mental retardation XL 55 56 KDM5C Mental retardation, syndromic, Claes-Jensen XL 47 55 KIAA2022 Mental retardation XL 42 40 KLF8 Intellectual disability XL 1 2 L1CAM Mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) XL 80 292 syndrome, Hydrocephalus due to congenital stenosis of aqueduct of Sylvius, Spastic, CRASH syndrome, Corpus callosum, partial agenesis LAMP2 Danon disease XL 62 101 MAGT1 Immunodeficiency, with magnesium defect, Epstein-Barr virus infection XL 8 14 and neoplasia, Mental retardation, X-linked 95 MAOA Brunner syndrome XL 7 14 MBTPS2 Keratosis follicularis spinulosa decalvans, IFAP syndrome, Palmoplantar XL 12 25 keratoderma, mutilating, with periorificial keratotic plaques MECP2 Angelman-like syndrome, Autism, Rett syndrome, Encephalopathy, Mental XL 506 1039 retardation MED12 Ohdo syndrome, Mental retardation, with Marfanoid habitus, FG XL 29 30 syndrome, Opitz-Kaveggia syndrome, Lujan-Fryns syndrome MID1* Opitz GBBB syndrome XL 30 96 MSL3 Mental retardation, X-linked XL 9 MTM1 Myopathy, centronuclear XL 158 301 NDP Exudative vitreoretinopathy, Norrie disease XL 31 167 NDUFA1 Mitochondrial complex I deficiency XL 3 4 NHS Nance-Horan syndrome, Cataract XL 36 52 NLGN3 Autism, Asperger syndrome XL 2 10 NLGN4X Autism, Asperger syndrome, Mental retardation XL 7 35 NONO Mental retardation, X-linked, syndrome 34, Left ventricular non- XL 10 4 compaction cardiomyopathy (LVNC) NSDHL Congenital hemidysplasia with ichthyosiform erythroderma and limb XL 15 28 defects (CHILD syndrome), CK syndrome NXF5* Familial heart block and focal segmental glomerulosclerosis, Mental XL 5 retardation, syndromic, X-linked OCRL Lowe syndrome, Dent disease XL 47 264 https://blueprintgenetics.com/ OFD1 Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital XL 153 160 syndrome, Joubert syndrome OPHN1 Mental retardation, with cerebellar hypoplasia and distinctive facial XL 28 42 appearance OTC Ornithine transcarbamylase deficiency XL 343 513 PAK3 Mental retardation XL 9 13 PCDH19 Epileptic encephalopathy, early infantile XL 116 200 PDHA1 Leigh syndrome, Pyruvate dehydrogenase E1-alpha deficiency XL 66 192 PGK1 Phosphoglycerate kinase 1 deficiency XL 16 26 PHF6 Borjeson-Forssman-Lehmann syndrome XL 22 29 PHF8 Mental retardation syndrome, Siderius XL 13 15 PLP1 Spastic paraplegia, Pelizaeus-Merzbacher disease XL 60 348 PORCN Focal dermal hypoplasia XL 16 121 PQBP1 Renpenning syndrome XL 14 18 PRPS1* Phosphoribosylpyrophosphate synthetase I superactivity, Arts syndrome, XL 27 32 Charcot-Marie-Tooth disease, X-linked recessive, 5, Deafness, X-linked 1 PTCHD1 Autism susceptibility, X-linked 4 XL 9 47 RAB39B Waisman parkinsonism-mental retardation syndrome, Mental retardation XL 6 17 RBM10 TARP syndrome XL 12 10 RLIM Mental retardation, X-linked 61 XL 4 5 RPL10 Autism XL 4 5 RPS6KA3 Coffin-Lowry syndrome, Mental retardation XL 65 171 SHROOM4 Stocco dos Santos mental retardation syndrome XL 4 9 SLC16A2 Allan-Herndon-Dudley syndrome XL 39 84 SLC6A8* Creatine deficiency syndrome XL 38 133 SLC9A6 Mental retardation, syndromic, Christianson XL 24 28 SMC1A Cornelia de Lange syndrome XL 73 87 SMS Mental retardation, Snyder-Robinson XL 11 14 SOX3 Panhypopituitarism XL 4 26 SRPX2 Rolandic epilepsy, mental retardation, and speech dyspraxia XL 3 4 SYN1 Epilepsy, with variable learning disabilities and behavior disorders XL 12 8 SYP Mental retardation XL 4 8 https://blueprintgenetics.com/ TAF1 Dystonia 3, torsion, X-linked, Mental retardation, X-linked, syndromic 33 XL 13 14 THOC2 Mental retardation, X-linked 12 XL 12 5 TIMM8A* Mohr-Tranebjaerg syndrome, Jensen syndrome, Opticoacoustic nerve XL 11 21 atrophy with dementia TSPAN7 Mental retardation XL 4 12 UBE2A Mental retardation, syndromic, Nascimento XL 9 25 UPF3B Mental retardation, syndromic XL 9 21 USP9X Mental retardation, X-linked 99, Mental retardation, X-linked 99, XL 30 27 syndromic, female restricted ZC4H2 Wieacker-Wolff syndrome XL 20 16 ZCCHC12 Intellectual disability XL 2 ZDHHC9 Mental retardation, syndromic, Raymond XL 9 14 ZNF41 Mental retardation XL 6 ZNF674 Mental retardation XL 7 ZNF711 Mental retardation XL 6 8 ZNF81 Mental retardation XL 3 3 *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 HGVS RefSeq RS-number HG19 ARHGEF6 ChrX:135861667 c.166-11T>C NM_004840.2
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  • Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences

    Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences

    Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences The Catalogue for Transmission Genetics in Arabs CTGA Database tRNA Methyltransferase 1, S. Cerevisiae, Homolog of Alternative Names planus. These findings are further bolstered by the TRMT1 fact that mutations in two other RNA- N2,N2-Dimethylguanosine-26 tRNA methyltransferase genes, NSUN2 and FTSJ1, have Methyltransferase been associated with intellectual disability. tRNA(m(2,2)G26)Dimethyltransferase Record Category Molecular Genetics Gene locus The TRMT1 gene is located on the short arm of chromosome 19 and spans a length of 12.6 kb of WHO-ICD DNA. Its coding sequence is spread across 18 N/A to gene loci exons and it encodes a 72.2 kDa protein product comprised of 659 amino acids. An additional 69.3 Incidence per 100,000 Live Births kDa isoform of the TRMT1 protein exists due to an N/A to gene loci alternatively spliced transcript variant. The gene is widely expressed in the human body, particularly in OMIM Number the nervous system, intestine, spleen, kidney and 611669 lung. Mode of Inheritance Epidemiology in the Arab World N/A to gene loci Saudi Arabia Monies et al. (2017) studied the findings of 1000 Gene Map Locus diagnostic panels and exomes carried out at a next 19p13.13 generation sequencing lab in Saudi Arabia. One patient, a 13-year-old male, presented with speech Description delay, intellectual disability, learning disability, The TRMT1 gene encodes a methyltransferase hypotonia and seizures. Using whole exome enzyme that acts on tRNA. This enzyme, which sequencing, a homozygous mutation consists of a zinc finger motif and an (c.1245_1246del, p.L415fs) was identified in exon arginine/proline rich region at its C-terminus, is 10 of the patient’s TRMT1 gene.