Your browser doesn't support javascript.
A homozygous variant disrupting the PIGH start-codon is associated with developmental delay, epilepsy, and microcephaly.
Hum Mutat ; 39(6): 822-826, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29573052
ABSTRACT
Defective glycosylphosphatidylinositol (GPI)-anchor biogenesis can cause a spectrum of predominantly neurological problems. For eight genes critical to this biological process, disease associations are not yet reported. Scanning exomes from 7,833 parent-child trios and 1,792 singletons from the DDD study for biallelic variants in this gene-set uncovered a rare PIGH variant in a boy with epilepsy, microcephaly, and behavioral difficulties. Although only 2/2 reads harbored this c.1A > T transversion, the presence of ∼25 Mb autozygosity at this locus implied homozygosity, which was confirmed using Sanger sequencing. A similarly-affected sister was also homozygous. FACS analysis of PIGH-deficient CHO cells indicated that cDNAs with c.1A > T could not efficiently restore expression of GPI-APs. Truncation of PIGH protein was consistent with the utilization of an in-frame start-site at codon 63. In summary, we describe siblings harboring a homozygous c.1A > T variant resulting in defective GPI-anchor biogenesis and highlight the importance of exploring low-coverage variants within autozygous regions.

Similares

MEDLINE

...
LILACS

LIS

Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Revista: Hum Mutat Assunto da revista: Genética Médica Ano de publicação: 2018 Tipo de documento: Artigo País de afiliação: Reino Unido