Heterozygous mutations in ZMYM2 were recently observed in 19 individuals presenting with a multisystem syndrome characterized by congenital anomalies of the kidney and urinary tract (CAKUT), cardiac defects, dysmorphic facial features, and/or neurological features, including 4 individuals with autism spectrum disorder and 2 others with stereotypy (Connaughton et al., 2020). Two de novo variants in ZMYM2 (one frameshift variant, one missense variant with a CADD score of 29.9) were reported in ASD probands from the SPARK cohort in Wang et al., 2020, while single-molecular molecular inversion probe (smMIP) sequencing of 125 genes in over 16,000 cases with neurodevelopmental disorders in the same report identified a number of ASD-associated likely gene-disruptive and missense variants with CADD scores 30, including a de novo frameshift variant in a proband from the Italian Autism Network (ITAN) cohort, in ZMYM2. A maternally-inherited likely gene-disruptive variant in ZMYM2 was transmitted to two of three ASD-affected siblings in a multiplex family from the iHART cohort in Russo et al., 2019.
Molecular Function
The protein encoded by this gene is a zinc finger protein that may act as a transcription factor. The encoded protein may be part of a BHC histone deacetylase complex.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations of the Transcriptional Corepressor ZMYM2 Cause Syndromic Urinary Tract Malformations
Congenital anomalies of the kidney and urinary tra
