IngentaConnect Novel EBP gene mutations in ConradiHunermannHapple syndrome

Authors: Steijlen, P.M.; van Geel, M.; Vreeburg, M.¹; Marcus-Soekarman, D.¹; Spaapen, L.J.M.; Castelijns, F.C.M.²; Willemsen, M.³; van Steensel, M.A.M.

Source: British Journal of Dermatology, Volume 157, Number 6, December 2007 , pp. 1225-1229(5)

Publisher: Blackwell Publishing

Abstract:

Summary Background

Conradi-Hünermann-Happle syndrome [X-linked dominant chondrodysplasia punctata type 2 (CDPX2); MIM no. 302960] is an X-linked dominant disorder of cholesterol metabolism that causes a wide spectrum of skeletal abnormalities and linear ichthyosiform skin lesions. Mosaicism is probably responsible for the variability of the phenotype. Objectives

To describe new mutations in patients with variable manifestations of the disease. Methods

We studied three patients with CDPX2. We performed mutation analysis of the EBP (formerly known as CDPX2) gene and gas chromatography-mass spectroscopy on serum of two patients. Results

We found two novel (3G→T and 419-422delTTCT) and one known mutation in the EBP gene. We demonstrated the presence of increased levels of dehydrocholesterol and 8(9)-cholestenol in the two patients with new mutations, confirming the diagnosis of CDPX2 and strongly suggesting that the mutations are indeed pathogenic. One patient had a very mild phenotype, presenting with linear alopecia and a mild symmetrical epiphyseal dysplasia. X-inactivation studies in peripheral blood of all patients showed skewing in only the most severely affected patient. Conclusions

The strong phenotypic variability in our patients suggests that there is no clear genotype-phenotype correlation.

Keywords: CDPX2; Conradi-Hünermann-Happle; EBP; mosaicism; X-inactivation

Document Type: Research article

DOI: 10.1111/j.1365-2133.2007.08254.x

Affiliations: 1: Clinical Genetics 2: Department of Dermatology, Elkerlyck Hospital Helmond, the Netherlands 3: Department of Pediatric Neurology, University Medical Center Nijmegen, the Netherlands

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$50.16 plus tax Refund Policy

Novel EBP gene mutations in Conradi-Hünermann-Happle syndrome