Brunet et al., 2020 delineated the genotypic and phenotypic spectrum of 25 individuals (15 males, 10 females) with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome) and found that 10/20 (50%) individuals had a diagnosis of autism spectrum disorder. De novo likely gene-disruptive (dnLGD) variants in the MSL3 gene were identified in an ASD proband from the SPARK cohort (Wang et al., 2020) and in four probands from the Deciphering Developmental Disorders study in 2017, while a de novo missense variant in MSL3 was identified in a female ASD proband from the Autism Sequencing Consortium in Satterstrom et al., 2020. Single-molecule molecular inversion probe (smMIP) sequencing of 125 genes in over 16,000 cases with neurodevelopmental disorders in Wang et al., 2020 identified an additional likely gene-disruptive variant in an ASD proband from the AGRE cohort.
This gene encodes a nuclear protein that is similar to the product of the Drosophila male-specific lethal-3 gene. The Drosophila protein plays a critical role in a dosage-compensation pathway, which equalizes X-linked gene expression in males and females. Thus, the human protein is thought to play a similar function in chromatin remodeling and transcriptional regulation, and it has been found as part of a complex that is responsible for histone H4 lysine-16 acetylation. Hemizygous or heterozygous mutations in the MSL3 gene are responsible for Basilicata-Akhtar syndrome (MRXSBA; OMIM 301032), a disorder characterized by global developmental delay apparent from infancy, feeding difficulties, hypotonia, and poor or absent speech (Basilicata et al., 2018).
Type of Disorder
Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder