Variants in CIB2 cause DFNB48 and not USH1J.
Clin Genet
; 93(4): 812-821, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-29112224
The genetic, mutational and phenotypic spectrum of deafness-causing genes shows great diversity and pleiotropy. The best examples are the group of genes, which when mutated can either cause non-syndromic hearing loss (NSHL) or the most common dual sensory impairment, Usher syndrome (USH). Variants in the CIB2 gene have been previously reported to cause hearing loss at the DFNB48 locus and deaf-blindness at the USH1J locus. In this study, we characterize the phenotypic spectrum in a multiethnic cohort with autosomal recessive non-syndromic hearing loss (ARNSHL) due to variants in the CIB2 gene. Of the 6 families we ascertained, 3 segregated novel loss-of-function (LOF) variants, 2 families segregated missense variants (1 novel) and 1 family segregated a previously reported pathogenic variant in trans with a frameshift variant. This report is the first to show that biallelic LOF variants in CIB2 cause ARNSHL and not USH. In the era of precision medicine, providing the correct diagnosis (NSHL vs USH) is essential for patient care as it impacts potential intervention and prevention options for patients. Here, we provide evidence disqualifying CIB2 as an USH-causing gene.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Unión al Calcio
/
Predisposición Genética a la Enfermedad
/
Síndromes de Usher
/
Pérdida Auditiva Sensorineural
Tipo de estudio:
Diagnostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Genet
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Dinamarca