title: SHOX nullizygosity and haploinsufficiency in a Japanese family: implication for the development of Turner skeletal features.
abstract: We report on clinical and molecular findings in a Japanese family consisting of a male infant with SHOX nullizygosity and his four family members with SHOX haploinsufficiency. The male infant had Langer mesomelic dysplasia, the prepubertal sister had idiopathic short stature phenotype with no discernible skeletal features, the father had mild Léri-Weill dyschondrosteosis (LWDC), and the mother and the maternal grandmother had moderate LWDC. The five subjects lacked clinically recognizable short metacarpals, cubitus valgus, high arched palate, short neck, and micrognathia, as well as recurrent otitis media and hearing loss. Fluorescence in situ hybridization and sequence analyses showed that the proband had a pseudoautosomal microdeletion involving SHOX and a C502T missense mutation in the homeobox domain at exon 4, and that the father was heterozygous for the SHOX deletion, and the sister, the mother, and the grandmother were heterozygous for the C502T mutation. The results, in conjunction with the previous findings, suggest that mesomelic skeletal features such as Langer mesomelic dysplasia and LWDC, which are absent or rare in Turner syndrome, are primarily caused by the SHOX dosage effect and the bone maturing effect of gonadal estrogens, whereas other skeletal features such as short metacarpals, cubitus valgus, and various craniofacial and cervical skeletal stigmata, which are common in Turner syndrome, are largely contributed by a compressive effect of distended lymphatics and lymphedema on the developing skeletal tissues.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan. t-ogata@po.iijnet.or.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Koji
authors.initials: K
authors.lastname: Muroya
authors.forename: Goro
authors.initials: G
authors.lastname: Sasaki
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitoh
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hattori
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002675:Child, Preschool; D003582:Cytogenetics; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011859:Radiography; D012016:Reference Values; D000074122:Short Stature Homeobox Protein; D014424:Turner Syndrome / Q000000981:diagnostic imaging
chemical_list: D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein