RESUMEN

Hoyeraal-Hreidarsson syndrome (HH) is a clinically severe variant of dyskeratosis congenita (DC), characterized by cerebellar hypoplasia, microcephaly, intrauterine growth retardation, and severe immunodeficiency in addition to features of DC. Germline mutations in the RTEL1 gene have recently been identified as causative of HH. In this study, the carrier frequency for five RTEL1 mutations that occurred in individuals of Ashkenazi Jewish descent was investigated in order to advise on including them in existing clinical mutation panels for this population. Our screening showed that the carrier frequency for c.3791G>A (p.R1264H) was higher than expected, 1% in the Ashkenazi Orthodox and 0.45% in the general Ashkenazi Jewish population. Haplotype analyses suggested the presence of a common founder. We recommend that the c.3791G>A RTEL1 mutation be considered for inclusion in carrier screening panels in the Ashkenazi population.

Asunto(s)

ADN Helicasas/genética , Disqueratosis Congénita/diagnóstico , Disqueratosis Congénita/genética , Retardo del Crecimiento Fetal/diagnóstico , Retardo del Crecimiento Fetal/genética , Tamización de Portadores Genéticos/métodos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Judíos/genética , Microcefalia/diagnóstico , Microcefalia/genética , Secuencia de Bases , Femenino , Pruebas Genéticas , Mutación de Línea Germinal , Haplotipos/genética , Humanos , Síndromes de Inmunodeficiencia/genética , Masculino , Polimorfismo de Nucleótido Simple/genética , Análisis de Secuencia de ADN