A 24-generation-old founder mutation impairs splicing of RBBP8 in Pakistani families affected with Jawad syndrome

Clin Genet. 2021 Oct;100(4):486-488. doi: 10.1111/cge.14028. Epub 2021 Jul 16.

Abstract

Jawad syndrome is a multiple congenital anomaly and intellectual disability syndrome with mutation in RBBP8 reported only in two families. Here, we report on two new families from Pakistan and identified a previously reported variant in RBBP8, NM_002894.3:c.1808-1809delTA. We could show that this mutation impairs splicing resulting in two different abnormal transcripts. Finally, we could verify a shared haplotype among all four families and estimate the founder event to have occurred some 24 generations ago.

Publication types

  • Case Reports
  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endodeoxyribonucleases / genetics*
  • Facies
  • Fingers / abnormalities*
  • Founder Effect*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Hand Deformities, Congenital / diagnosis*
  • Hand Deformities, Congenital / genetics*
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Microcephaly / diagnosis*
  • Microcephaly / genetics*
  • Mutation*
  • Pakistan
  • Pedigree
  • Phenotype
  • RNA Splicing*
  • Sequence Analysis, DNA
  • Toes / abnormalities*
  • Whole Exome Sequencing

Substances

  • Endodeoxyribonucleases
  • RBBP8 protein, human

Supplementary concepts

  • Microcephaly with Mental Retardation and Digital Anomalies