Exome sequencing reveals three homozygous missense variants in SNRPA in two sisters with syndromic intellectual disability.

Autor: Rangel-Sosa MM; Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico., Figuera-Villanueva LE; División de Genética, Centro de Investigación Biomédica de Occidente, CMNO-IMSS, Guadalajara, Mexico.; Doctorado en Genética Humana, CUCS-Universidad de Guadalajara, Guadalajara, Mexico., González-Ramos IA; Departamento de Genética, Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, Mexico., Pérez-Páramo YX; Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico., Martínez-Jacobo LA; Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico., Arnaud-López L; Genética Médica, División de Pediatría, Nuevo Hospital Civil 'Dr. Juan I. Menchaca', Guadalajara, Mexico., Nastasi-Catanese JA; Núcleo Bolívar, Universidad de Oriente, Ciudad Bolívar, Venezuela., Rivas-Estilla AM; Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico., Galán-Huerta KA; Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico., Rojas-Martínez A; Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Mexico., Ortiz-López R; Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Mexico., Córdova-Fletes C; Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2018 Jun; Vol. 93 (6), pp. 1229-1233. Date of Electronic Publication: 2018 Mar 09.
DOI: 10.1111/cge.13235
Abstrakt: Splicing-related gene mutations might affect the expression of a single gene or multiple genes and cause clinically heterogeneous diseases. With the advent of next-generation sequencing, several splicing gene mutations have been exposed, yet most major spliceosome genes have no reports of germline mutations and therefore, their effects are largely unknown. We describe the previously unreported concurrence of intellectual disability, short stature, poor speech, and minor craniofacial and hand anomalies in 2 female siblings with 3 homozygous missense variants in SNRPA (a component of the U1 small nuclear ribonucleoprotein complex) characterized by homozygosity mapping and whole exome sequencing. Combined, c.97A>G, c.98T>C, and c.100T>A, in exon 2 of SNRPA lead to p.Ile33Ala and p.Phe34Ile exchanges, which were predicted in silico to be deleterious. Although both patients exhibited some clinical features seen in other spliceosomal disorders, their complete clinical phenotype appears to be rather uncommon, a finding that may further support the notion that mutations in components of the major spliceosome do not strictly lead to the same syndromes/phenotypes.
(© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE