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Characterization of a novel non-canonical splice site variant (c.886-5T>A) in NBAS and description of the associated phenotype.
Priglinger, Claudia S; Rudolph, Günter; Schmid, Irene; Mazzola, Pascale; Haack, Tobias B; Reith, Milda; Stingl, Katarina; Weisschuh, Nicole.
Afiliación
  • Priglinger CS; University Eye Hospital, Ludwig Maximilians University of Munich, Munich, Germany.
  • Rudolph G; University Eye Hospital, Ludwig Maximilians University of Munich, Munich, Germany.
  • Schmid I; Department of Pediatrics, Division of Pediatric Hematology and Oncology, Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
  • Mazzola P; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
  • Haack TB; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
  • Reith M; Centre for Rare Diseases, University of Tübingen, Tübingen, Germany.
  • Stingl K; Centre for Ophthalmology, University Eye Hospital, University of Tübingen, Tübingen, Germany.
  • Weisschuh N; Centre for Ophthalmology, University Eye Hospital, University of Tübingen, Tübingen, Germany.
Mol Genet Genomic Med ; 11(3): e2120, 2023 03.
Article en En | MEDLINE | ID: mdl-36479642
BACKGROUND: Biallelic pathogenic variants in the neuroblastoma-amplified sequence (NBAS) gene manifest in a broad spectrum of disorders, including, but not limited to recurrent acute liver failure, skeletal dysmorphism, susceptibility to infections, and SOPH syndrome with its cardinal symptoms of short stature, optic atrophy, and Pelger-Huët anomaly. We aimed to present clinical and genetic characteristics of two sisters (20 and 15 years old) who were diagnosed with optic atrophy and cone dystrophy in childhood. Genome sequencing revealed two novel variants in NBAS in compound heterozygous state in both sisters, namely a 1-bp deletion predicted to result in a premature termination codon (c.5104del; p.(Met1702*)), and a non-canonical splice site variant of unclear significance (c.886-5T>A; p.?). RESULTS: Clinical examination and history revealed cone dystrophy, optic atrophy, and Pelger-Huët anomaly, but no short stature, recurrent acute liver failure, or susceptibility to infections. RNA analysis revealed that the c.886-5T>A variant results in two aberrant transcripts that are predicted to lead to in frame amino acid changes in the ß-propeller region of the protein. CONCLUSION: We hypothesize that the phenotype of our subjects, which appears to be at the end of the spectrum of NBAS-related disorders, could be explained by residual protein function mediated by the non-canonical splice site variant c.886-5T>A. Our study contributes to the existing knowledge on the genotypic and phenotypic spectrum of NBAS-related disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anomalía de Pelger-Huët / Atrofia Óptica / Fallo Hepático Agudo / Enanismo / Distrofia del Cono / Neuroblastoma Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Mol Genet Genomic Med Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anomalía de Pelger-Huët / Atrofia Óptica / Fallo Hepático Agudo / Enanismo / Distrofia del Cono / Neuroblastoma Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Mol Genet Genomic Med Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos