Loss-of-function variants in ARHGEF9 are associated with an X-linked intellectual disability dominant disorder.
Hum Mutat
; 42(5): 498-505, 2021 05.
Article
en En
| MEDLINE
| ID: mdl-33600053
ABSTRACT
ARHGEF9 defects lead to an X-linked intellectual disability disorder related to inhibitory synaptic dysfunction. This condition is more frequent in males, with a few affected females reported. Up to now, sequence variants and gross deletions have been identified in males, while only chromosomal aberrations have been reported in affected females who showed a skewed pattern of X-chromosome inactivation (XCI), suggesting an X-linked recessive (XLR) disorder. We report three novel loss-of-function (LoF) variants in ARHGEF9 A de novo synonymous variant affecting splicing (NM_015185.2 c.1056G>A, p.(Lys352=)) in one female; a nonsense variant in another female (c.865C>T, p.(Arg289*)), that is, also present as a somatically mosaic variant in her father, and a de novo nonsense variant in a boy (c.899G>A; p.(Trp300*)). Both females showed a random XCI. Thus, we suggest that missense variants are responsible for an XLR disorder affecting males and that LoF variants, mainly occurring de novo, may be responsible for an X-linked dominant disorder affecting males and females.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Discapacidad Intelectual
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
/
Male
Idioma:
En
Año:
2021
Tipo del documento:
Article