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Acampomelic campomelic dysplasia; Deletion; Sex reversal; SOX9; Translocation
Abstract:
Campomelic dysplasia (MIM 114290) is a severe malformation
syndrome frequently accompanied by male-to-female
sex reversal. Causative are mutations within the SOX9 gene
on 17q24.3 as well as chromosomal aberrations (translocations,
inversions or deletions) in the vicinity of SOX9 . Here, we
report on a patient with muscular hypotonia, craniofacial
dysmorphism, cleft palate, brachydactyly, malformations of
thoracic spine, and gonadal dysgenesis with female external
genitalia and müllerian duct derivatives in the presence
of a male karyotype. X-ray examination and clinical examinations revealed no signs of campomelia. The combination of molecular cytogenetic analysis and array CGH revealed
an unbalanced translocation between one chromosome 7
and one chromosome 17 [46,XY,t(7; 17)(q33;q24).ish t(7; 17)
(wcp7+,wcp17+;wcp7+wcp17+)] with a deletion of approximately
4.2 Mb located about 0.5 Mb upstream of SOX9 . STS
analysis confirmed the deletion of chromosome 17, which
has occurred de novo on the paternal chromosome. The
proximal breakpoint on chromosome 17 is localized outside the known breakpoint cluster regions. The deletion on chromosome 17q24 removes several genes. Among these genes PRKAR1A is deleted. Inactivating mutations of PRKAR1A cause Carney complex. To our knowledge, this is the first report of a patient with acampomelic campomelic dysplasia, carrying
both a deletion and a translocation.
