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.
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.
Authors: Massimiliano Rossi; Christine M Hall; Raymonde Bouvier; Sophie Collardeau-Frachon; Frédérique Le Breton; Martine Bucourt; Marie Pierre Cordier; Christine Vianey-Saban; Giancarlo Parenti; Generoso Andria; Martine Le Merrer; Patrick Edery; Amaka C Offiah Journal: Pediatr Radiol Date: 2015-02-03
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