title: Diversified clinical presentations associated with a novel sal-like 4 gene mutation in a Chinese pedigree with Duane retraction syndrome.
abstract: OBJECTIVE
  To determine the underlying genetic cause of Duane retraction syndrome (DRS) in a non-consanguineous Chinese Han family.
  
  
  METHODS
  Detailed ophthalmic and physical examinations were performed on all members from a pedigree with DRS. All exons and their adjacent splicing junctions of the sal-like 4 (SALL4) gene were amplified with polymerase chain reaction and analyzed with direct sequencing in all the recruited family members and 200 unrelated control subjects.
  
  
  RESULTS
  Clinical examination revealed a broad spectrum of phenotypes in the DRS family. Mutation analysis of SALL4 identified a novel heterozygous duplication mutation, c.1919dupT, which was completely cosegregated with the disease in the family and absent in controls. This mutation was predicted to cause a frameshift, introducing a premature stop codon, when translated, resulting in a truncated SALL4 protein, i.e., p.Met640IlefsX25. Bioinformatics analysis showed that the affected region of SALL4 shared a highly conserved sequence across different species. Diversified clinical manifestations were observed in the c.1919dupT carriers of the family.
  
  
  CONCLUSIONS
  We identified a novel truncating mutation in the SALL4 gene that leads to diversified clinical features of DRS in a Chinese family. This mutation is predicted to result in a truncated SALL4 protein affecting two functional domains and cause disease development due to haploinsufficiency through nonsense-mediated mRNA decay.
authors.affiliation: Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, and Department of Ophthalmology, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Ming-ming
authors.initials: MM
authors.lastname: Yang
authors.forename: Mary
authors.initials: M
authors.lastname: Ho
authors.forename: Henry H W
authors.initials: HH
authors.lastname: Lau
authors.forename: Pancy O S
authors.initials: PO
authors.lastname: Tam
authors.forename: Alvin L
authors.initials: AL
authors.lastname: Young
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
authors.forename: Wilson W K
authors.initials: WW
authors.lastname: Yip
authors.forename: LiJia
authors.initials: L
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D004370:Duane Retraction Syndrome / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005403:Fixation, Ocular / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
chemical_list: C472575:SALL4 protein, human; D014157:Transcription Factors