title: Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family.
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.
authors.affiliation: Department of Neurology, Children's Hospital Boston, Harvard Medical School, MA 02115, USA.
authors.forename: Raidah
authors.initials: R
authors.lastname: Al-Baradie
authors.forename: Koki
authors.initials: K
authors.lastname: Yamada
authors.forename: Cynthia
authors.initials: C
authors.lastname: St  Hilaire
authors.forename: Wai-Man
authors.initials: WM
authors.lastname: Chan
authors.forename: Caroline
authors.initials: C
authors.lastname: Andrews
authors.forename: Nathalie
authors.initials: N
authors.lastname: McIntosh
authors.forename: Motoi
authors.initials: M
authors.lastname: Nakano
authors.forename: E Jean
authors.initials: EJ
authors.lastname: Martonyi
authors.forename: William R
authors.initials: WR
authors.lastname: Raymond
authors.forename: Sada
authors.initials: S
authors.lastname: Okumura
authors.forename: Michael M
authors.initials: MM
authors.lastname: Okihiro
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Engle
mesh_terms: D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D004370:Duane Retraction Syndrome / Q000235:genetics*; D005260:Female; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers
chemical_list: C472575:SALL4 protein, human; D014157:Transcription Factors