Oculocutaneous albinism variants in 28 consanguineous families and functional classification of a pathogenic deep intron variant in TYR
Farooq, M.; Bruun, G. H.; Sarusie, M. V. K.; Kessel, L.; Akhtar, H.; Abdullah, U.; Anjum, I.; Doktor, T. K.; Andresen, B. S.; Baig, S. M.; Larsen, L. A.; Gronskov, K.
Show abstract
Oculocutaneous albinism (OCA) is genetically and clinically heterogeneous recessive disorders with at least 23 associated genes. Isolated OCA is characterized by hypopigmentation in the skin, hair, and eyes combined with ocular abnormalities. Hermansky Pudlak syndrome (HPS) and Chediak-Higaski syndrome are syndromic forms of OCA, distinguished by immunological and hematological symptoms in addition to hypopigmentation and ocular anomalies. Targeted clinical care is crucial for the patients and molecular genetic diagnosis is important for classification of patients. Current diagnostic yield is approximately 70%, and a high prevalence of patients, heterozygous for pathogenic variants in OCA genes, might suggest presence of disease-causing non-coding variants. We describe here NGS analysis, including CNV analysis, of 28 consanguineous families, comprising a total of 136 individuals presenting with OCA. We provide a molecular genetic diagnosis in all 28 families. Noteworthy, five families (18 %) had pathogenic variants in a gene associated with HPS. Furthermore, we report the first deep intron variant in TYR causing OCA and show by minigene analysis that the variant causes inclusion of a pseudoexon.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Splicing impact of deep exonic missense variants in CAPN3 explored systematically by minigene functional assay 94%
- Spectrum of pathogenic variants and multiple founder effects in amelogenesis imperfecta associated with MMP20 94%
- Using single molecule Molecular Inversion Probes as a cost-effective, high-throughput sequencing approach to target all genes and loci associated with macular diseases 93%
Similar papers in this journal
- A comparative medical genomics approach may facilitate the interpretation of rare missense variation 93%
- Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases 92%
- Exome sequencing as a first-tier test for copy number variant detection : retrospective evaluation and prospective screening in 2418 cases 92%
Similar papers in this journal
- Structural variant calling and clinical interpretation in 6224 unsolved rare disease exomes 94%
- Axenfeld-Rieger syndrome associated with a megabase-scale inversion separating PITX2 from a conserved enhancer locus 92%
- BCL11A intellectual developmental disorder: defining the clinical spectrum and genotype-phenotype correlations 92%
Similar papers in this journal
- Resolving the diagnostic odyssey in inherited retinal dystrophies through long-read genome sequencing 95%
- Rare variants found in multiplex families with orofacial clefts: Does expanding the phenotype make a difference? 94%
- Next-generation phenotyping in Nigerian children with Cornelia de Lange Syndrome 94%
Similar papers in this journal
- Novel Loss-of-Function Mutations in COCH Cause Autosomal Recessive Nonsyndromic Deafness 93%
- PKHD1L1 , A Gene Involved in the Stereociliary Coat, Causes Autosomal Recessive Nonsyndromic Hearing Loss 93%
- Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.