title: Okihiro syndrome is caused by SALL4 mutations.
abstract: Okihiro syndrome refers to the association of forearm malformations with Duane syndrome of eye retraction. Based on the reported literature experience, clinical diagnosis of the syndrome can be elusive, owing to the variable presentation in families reported. Specifically, there is overlap of clinical features with other conditions, most notably Holt-Oram syndrome, a condition resulting from mutation of the TBX5 locus and Townes-Brocks syndrome, known to be caused by mutations in the SALL1 gene. Arising from our observation of several malformations in Okihiro syndrome patients which are also described in Townes-Brocks syndrome, we postulated that Okihiro syndrome might result from mutation of another member of the human SALL gene family. We have characterized the human SALL4 gene on chromosome 20q13.13-q13.2. Moreover, we have identified literature reports of forelimb malformations in patients with cytogenetically identifiable abnormalities of this region. We here present evidence in 5 of 8 affected families that mutation at this locus results in the Okihiro syndrome phenotype.
authors.affiliation: Institut für Humangenetik, Universität Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany. jkohlha@gwdg.de
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kohlhase
authors.forename: Marielle
authors.initials: M
authors.lastname: Heinrich
authors.forename: Lucia
authors.initials: L
authors.lastname: Schubert
authors.forename: Manuela
authors.initials: M
authors.lastname: Liebers
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
authors.forename: Franco
authors.initials: F
authors.lastname: Laccone
authors.forename: Peter
authors.initials: P
authors.lastname: Turnpenny
authors.forename: Robin M
authors.initials: RM
authors.lastname: Winter
authors.forename: William
authors.initials: W
authors.lastname: Reardon
mesh_terms: D016022:Case-Control Studies; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D004370:Duane Retraction Syndrome / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics; D005260:Female; D006228:Hand Deformities, Congenital / Q000235:genetics; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: C472575:SALL4 protein, human; D014157:Transcription Factors