Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability.
Eur J Hum Genet
; 27(2): 278-290, 2019 02.
Article
en En
| MEDLINE
| ID: mdl-30291340
ABSTRACT
Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate, typically co-occurring with intellectual disability, facial dysmorphism, and congenital heart defects. The identification of patients with loss-of-function variants in MEIS2, a gene within this deletion, suggests that these features are attributed to haploinsufficiency of MEIS2. To further delineate the phenotypic spectrum of the MEIS2-related syndrome, we collected 23 previously unreported patients with either a de novo sequence variant in MEIS2 (9 patients), or a 15q14 microdeletion affecting MEIS2 (14 patients). All but one de novo MEIS2 variant were identified by whole-exome sequencing. One variant was found by targeted sequencing of MEIS2 in a girl with a clinical suspicion of this syndrome. In addition to the triad of palatal defects, heart defects, and developmental delay, heterozygous loss of MEIS2 results in recurrent facial features, including thin and arched eyebrows, short alae nasi, and thin vermillion. Genotype-phenotype comparison between patients with 15q14 deletions and patients with sequence variants or intragenic deletions within MEIS2, showed a higher prevalence of moderate-to-severe intellectual disability in the former group, advocating for an independent locus for psychomotor development neighboring MEIS2.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Fisura del Paladar
/
Proteínas de Homeodominio
/
Mutación con Pérdida de Función
/
Cardiopatías Congénitas
/
Discapacidad Intelectual
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Hum Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Bélgica