Whole-exome sequencing of a Turkish cohort of 62 children diagnosed with ASD or at risk for ASD in Eser et al., 2025 identified a homozygous missense variant in the MAN1B1 gene (p.Arg334Cys) in a 7-year-old male born to consanguineous parents; this variant has previously been shown to cause reduced protein expression and other functional deficits in both HEK293 cells and patient-derived fibroblasts (Rafiq et al., 2011; Rymen et al., 2013). A different homozygous missense variant in MAN1B1 (p.Val633Phe) had previously been reported in a female ASD proband from Saudi Arabia (Al-Mubarak et al., 2017). A diagnosis of ASD was made in one of seven individuals presenting with Rafiq syndrome in Rymen et al., 2013, while behavioral abnormalities (including autistic features) were observed in a subset of 12 individuals with Rafiq syndrome described in Van Scherpenzeel et al., 2014. De novo and inherited heterozygous variants in this gene have also been observed in ASD probands from the MSSNG cohort, the SPARK cohort, and the mAGRE cohort (Yuen et al., 2017; Trost et al., 2022; Cirnigliaro et al., 2023).
Molecular Function
This gene encodes an enzyme belonging to the glycosyl hydrolase 47 family. This enzyme functions in N-glycan biosynthesis, and is a class I alpha-1,2-mannosidase that specifically converts Man9GlcNAc to Man8GlcNAc isomer B. It is required for N-glycan trimming to Man5-6GlcNAc2 in the endoplasmic-reticulum-associated degradation pathway. Mutations in this gene cause a form of autosomal-recessive intellectual disability (Rafiq syndrome, OMIM 614202) (Rafiq et al., 2011).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Multilayered genetic dissection of autism: insights from whole-exome sequencing, molecular karyotyping, and cytogenetic analyses in a small Turkish cohort
