title: Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.
abstract: Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects.
authors.affiliation: Human Genome Laboratory, Department of Human Genetics, KU Leuven, Leuven, Belgium; Human Genome Laboratory, VIB Center for the Biology of Disease, Leuven, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Bauters
authors.forename: Suzanna G
authors.initials: SG
authors.lastname: Frints
authors.forename: Hilde
authors.initials: H
authors.lastname: Van Esch
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Spruijt
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Baldewijns
authors.forename: Christine E M
authors.initials: CE
authors.lastname: de Die-Smulders
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Peter
authors.initials: P
authors.lastname: Marynen
authors.forename: Guy
authors.initials: G
authors.lastname: Froyen
mesh_terms: D000293:Adolescent; D000328:Adult; D058674:Chromosome Duplication; D002874:Chromosome Mapping; D020090:Chromosome Segregation; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D050172:Genes, X-Linked; D005838:Genotype; D006801:Humans; D007018:Hypopituitarism / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009436:Neural Tube Defects / Q000235:genetics*; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D012307:Risk Factors; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C527785:SOX3 protein, human; D055748:SOXB1 Transcription Factors
keywords: SOX3 duplication; X-linked hypopituitarism; gene overexpression; growth hormone deficiency; neural tube defect