A Palindrome-Like Structure on 16p13.3 Is Associated with the Formation of Complex Structural Variations and <i>SRRM2</i> Haploinsufficiency.

ABSTRACT: SRRM2 encodes a splicing factor recently implicated in developmental disorders due to a statistical enrichment of de novo mutations. Using data from the 100,000 Genomes Project, four unrelated individuals with intellectual disability (ID) were identified, each harbouring de novo whole gene deletions of SRRM2. Deletions ranged between 248 and 482 kb in size and all distal breakpoints clustered within a complex 144 kb palindrome situated 75 kb upstream of SRRM2. Strikingly, three of the deletions were complex, with inverted internal segments of 45-94 kb. In one proband-mother duo, de novo status was inferred by haplotype analysis. Together with two additional patients who harboured smaller predicted protein-truncating variants (p.Arg632^∗ and p.Ala2223Leufs

SUBMITTER: Pagnamenta AT 

PROVIDER: S-EPMC11918891 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature