Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder.
Genet Med
; 23(2): 384-395, 2021 02.
Article
en En
| MEDLINE
| ID: mdl-33173220
ABSTRACT
PURPOSE:
We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome).METHODS:
Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers.RESULTS:
We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined.CONCLUSION:
Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Trastorno del Espectro Autista
/
Discapacidad Intelectual
Tipo de estudio:
Guideline
/
Prognostic_studies
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2021
Tipo del documento:
Article