Autosomal Recessive ID and ASD
CC2D2A
Our research identified a homozygous splice-site mutation in the CC2D2A gene as the cause of autosomal recessive intellectual disability and retinitis pigmentosa in a consanguineous family from Punjab, Pakistan—linking the condition to Joubert syndrome, a ciliopathy characterized by the “molar tooth sign” on brain imaging.
DCPS and EDC3
Our research identified DCPS and EDC3 mutations causing autosomal recessive intellectual disability, implicating defects in mRNA degradation pathways in neurodevelopment. DCPS and EDC3 mutations impaired decapping activity, and some affected individuals also showed myopathy.
FMN2
Our research identified FMN2 as a gene for non-syndromic autosomal recessive intellectual disability using homozygosity mapping and whole-exome sequencing in Pakistani and Egyptian families. Homozygous truncating mutations in FMN2 were found, and the locus is now listed in OMIM as MRT47.
HNMT
Our research identified homozygous missense mutations in HNMT causing non-syndromic autosomal recessive intellectual disability in two consanguineous families of Kurdish and Turkish origin. The study also suggested that heterozygous truncating mutations or CNVs disrupting HNMT may increase risk for ASD, ID, schizophrenia, and bipolar disorder.
NSUN2
Khan et al. (2012) identified NSUN2 mutations causing autosomal recessive intellectual disability, with the p.Gly679Arg variant disrupting nucleolar localization of the protein.
TCTN2
We identified homozygous TCTN2 mutations causing Joubert syndrome in Pakistani, Turkish, and Indian families, confirmed by the molar tooth sign on MRI. These findings, along with ATXN10 mutations in another Joubert family, were reported in Cell (2012).
TRAPPC9
In 2009, TRAPPC9 (NIBP/MRT13) was identified as a gene for non-syndromic autosomal recessive intellectual disability, with mutations reported in families from Pakistan, Iran, and Italy. More recently, compound heterozygous mutations were found in a Thai autism family.