Reduced penetrance in a family with X-linked dominant chondrodysplasia punctata.
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.
Hellenbroich
Yorck
Y
Institut für Humangenetik, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. yorck.hellenbroich@uk-sh.de
Grzeschik
Karl-Heinz
KH
Krapp
Martin
M
Jarutat
Tiantom
T
Lehrmann-Petersen
Christa
C
Buiting
Karin
K
Gillessen-Kaesbach
Gabriele
G
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
D018389:Codon, Nonsense; D013251:Steroid Isomerases; C090445:EBP protein, human