C. Has et al., The Conradi-Hunermann-Happle syndrome (CDPX2) and emopamil binding protein: novel mutations, and somatic and gonadal mosaicism, HUM MOL GEN, 9(13), 2000, pp. 1951-1955
The Conradi-Hunermann-Happle (CHH) syndrome (X-chromosomal dominant chondro
dysplasia punctata type II; MIM 302960) is an X-linked dominant disorder th
at is characterized by ichthyosis, chondrodysplasia punctata, cataracts and
short stature. The disease occurs almost exclusively in females and shows
increased disease expression in successive generations (anticipation), Rece
ntly, causative mutations in the emopamil binding protein (EBP) have been i
dentified. To better appreciate the genetics of this syndrome we analyzed t
he ESP gene in seven independent families using PCR, conformation-sensitive
gel electrophoresis, direct sequencing and restriction enzyme analysis. We
found five novel mutations: three nonsense mutations in exon 2 and exon 3
and two frameshift mutations, one deletion in exon 4 and an insertion in ex
on 5, In two families, known mutations affecting exon 2 were identified, Su
rprisingly, we failed to detect the mutation in a grandmother exhibiting mi
nor disease symptoms such as sectorial cataract and attribute this to gonad
al and somatic mosaicism, Gonadal mosaicism appeared also to be involved in
the case of healthy parents having two affected girls, one of whom died du
e to the disease, We conclude that gonadal mosaicism has to be considered w
hen dealing with seemingly sporadic cases.