Identifying SHROOM4 as a novel X-linked susceptibility gene for cerebral palsy in Chinese males.
SHROOM4 haplotype linked to over 6-fold higher odds of male cerebral palsy
Identifying SHROOM4 as a novel X-linked susceptibility gene for cerebral palsy in Chinese males.
Cerebral palsy (cerebral palsy) is a leading cause of childhood motor disability with a notable male predominance, suggesting that X-linked genetic factors may contribute to cerebral palsy susceptibility.
This study aimed to investigate the contribution of SHROOM4 variants to male cerebral palsy susceptibility.
Whole-exome sequencing was performed in 1,010 Chinese male patients with sporadic cerebral palsy and 1,014 male controls.
Additionally, a rare nonsense variant, c.
C2050T (p.
Functional analyses showed that p.
Arg684* and a population-derived frameshift variant (p.
Our findings support SHROOM4 as an X-linked susceptibility gene associated with male cerebral palsy, suggesting that both common haplotypes and rare SHROOM4 variants may contribute to the genetic susceptibility to cerebral palsy.
These results expand our current understanding of the genetic architecture of cerebral palsy and highlight cytoskeletal regulation as a potentially relevant mechanism associated with SHROOM4 variants.