Duane Radial Ray Syndrome (Okihiro Syndrome) Maps to 20q13 and Results From Mutations in SALL4, a New Member of the SAL Family

Am J Hum Genet. 2002 Nov;71(5):1195-9. doi: 10.1086/343821. Epub 2002 Oct 22.

Abstract

Duane syndrome is a congenital eye movement disorder characterized most typically by absence of abduction, restricted adduction, and retraction of the globe on attempted adduction. Duane syndrome can be coinherited with radial ray anomalies as an autosomal dominant trait, referred to as "Okihiro syndrome" or "Duane radial ray syndrome" (DRRS). We ascertained three pedigrees with DRRS and mapped their disease gene to a 21.6-cM region of chromosome 20 flanked by markers D20S888 and D20S102. A new member of the SAL family of proposed C(2)H(2) zinc finger transcription factors, SALL4, falls within the region. Mutation analysis of SALL4 in the three pedigrees revealed one nonsense and two frameshift heterozygous mutations. SALL4 represents the first identified Duane syndrome gene and the second malformation syndrome resulting from mutations in SAL genes and likely plays a critical role in abducens motoneuron development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Mapping
  • Chromosomes, Human, Pair 20*
  • Duane Retraction Syndrome / genetics*
  • Female
  • Humans
  • Lod Score
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Sequence Analysis, DNA
  • Sequence Analysis, Protein
  • Transcription Factors / genetics*
  • Zinc Fingers

Substances

  • SALL4 protein, human
  • Transcription Factors

Associated data

  • OMIM/126800
  • OMIM/604356
  • RefSeq/NM_020436
  • RefSeq/NP_002959
  • RefSeq/NP_065169
  • RefSeq/NT_011362
  • RefSeq/XP_033473