title: Campomelic dysplasia without sex reversal in a Turkish patient is due to mutation Ala119Val within the SOX9 gene.
abstract: Campomelic dysplasia is a rare neonatal skeletal malformation syndrome mainly characterized by congenital bowing and angulation of long bones in combination with other skeletal and extraskeletal defects. Two thirds of karyotypic males exhibit male-to-female sex reversal. Point mutations within SOX9 in 17q24-25 or rearrangements upstream to SOX9 as well as a deletion of a complete gene, causing haploinsufficiency of the gene product, have been detected in some patients. Recurrent mutations appear to be rare and most mutations detected in campomelic dysplasia are family specific. Here, we report on a Turkish patient with a 46,XY karyotype affected by campomelic dysplasia without sex reversal. Sequencing the SOX9 gene revealed a heterozygous Ala119Val mutation in exon 1, coding for the highly conserved HMG-box of the gene. This mutation is not present in the parents' lymphocyte DNAs. The same mutation was recently reported in a patient with 46,XX karyotype. Additionally, our patient is homozygous for the common polymorphism c507C-->T, while both parents are heterozygous.
authors.affiliation: Department of Human Genetics, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany. sibylle.jakubiczka@medizin.uni-magdeburg.de
authors.forename: S
authors.initials: S
authors.lastname: Jakubiczka
authors.forename: T
authors.initials: T
authors.lastname: Bettecken
authors.forename: G
authors.initials: G
authors.lastname: Koch
authors.forename: B
authors.initials: B
authors.lastname: Tüysüz
authors.forename: B
authors.initials: B
authors.lastname: Wollnik
authors.forename: P
authors.initials: P
authors.lastname: Wieacker
mesh_terms: D002675:Child, Preschool; D004252:DNA Mutational Analysis; D012734:Disorders of Sex Development; D024742:HMG-Box Domains / Q000235:genetics; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D010009:Osteochondrodysplasias / Q000235:genetics*; D010290:Parents; D017354:Point Mutation; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D014421:Turkey
chemical_list: D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors