title: Reduced penetrance in a family with X-linked dominant chondrodysplasia punctata.
abstract: X-linked dominant chondrodysplasia punctata (Conradi-Hünermann disease, CDPX2) is characterised by short stature, stippled epiphyses, cataracts, ichthyosiform erythroderma and patchy alopecia of the scalp. The disorder is caused by mutations within the emopamil binding protein (EBP) gene encoding a 3beta-hydroxysteroid-Delta(8),Delta(7)-isomerase. The intrafamilial variation of disease severity is a known feature of CDPX2 probably caused by skewed X-inactivation. We report on a female fetus with typical symptoms of CDPX2 such as short limbs, postaxial polydactyly, ichthyotic skin lesions and punctate calcifications. Molecular genetic analysis of the EBP gene revealed a nonsense mutation (c.328C>T, p.R110X), which was previously detected in one CDPX2 patient and in a second female patient, who was only affected on one body side and erroneously diagnosed as CHILD syndrome. Surprisingly, the mother of our fetus carries the same mutation without having any signs of CDPX2. X-inactivation studies did not reveal any evidence of skewing neither in the mother nor in the fetus.
authors.affiliation: Institut für Humangenetik, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. yorck.hellenbroich@uk-sh.de
authors.forename: Yorck
authors.initials: Y
authors.lastname: Hellenbroich
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Grzeschik
authors.forename: Martin
authors.initials: M
authors.lastname: Krapp
authors.forename: Tiantom
authors.initials: T
authors.lastname: Jarutat
authors.forename: Christa
authors.initials: C
authors.lastname: Lehrmann-Petersen
authors.forename: Karin
authors.initials: K
authors.lastname: Buiting
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
mesh_terms: D000328:Adult; D002806:Chondrodysplasia Punctata / Q000201:enzymology / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics; D018389:Codon, Nonsense; D005260:Female; D005799:Genes, Dominant; D040181:Genetic Diseases, X-Linked / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D019683:Penetrance; D010641:Phenotype; D011247:Pregnancy; D011296:Prenatal Diagnosis; D013251:Steroid Isomerases / Q000235:genetics; D049951:X Chromosome Inactivation
chemical_list: D018389:Codon, Nonsense; D013251:Steroid Isomerases; C090445:EBP protein, human