1. ¹Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Philadelphia, Pennsylvania, USA
2. ²Pediatric Dermatology Unit, Hospital Jose Maria Ramos, Mejia, Buenos Aires, Argentina
3. ³Department of Dermatology, Mt Sinai School of Medicine, New York, New York, USA

Correspondence: Dr Franziska Ringpfeil, Department of Dermatology and Cutaneous Biology, Jefferson Medical College, 233 S. 10th Street, Suite 450 BLSB, Philadelphia, Pennsylvania 19107, USA. E-mail: franziska.ringpfeil@jefferson.edu

⁴These authors have contributed equally to this work

Received 16 June 2005; Revised 17 October 2005; Accepted 24 October 2005; Published online 12 January 2006.

Abstract

Pseudoxanthoma elasticum (PXE) is caused by mutations in the ABCC6 gene. Historically, PXE has been suggested to be inherited either in an autosomal dominant or autosomal recessive manner. To determine the exact mode of inheritance of PXE and to address the question of phenotypic expression in mutation carriers, we identified seven pedigrees with affected individuals in two different generations and sequenced the entire coding region of ABCC6 in affected individuals, presumed carriers with a limited phenotype and unaffected family members. Two allelic mutations were identified in each individual with unambiguous diagnosis of PXE, as well as in those with only minimal clinical signs suggestive of PXE but with positive skin biopsy. Missense mutations were frequently detected in the latter cases. In conclusion, PXE is inherited in an autosomal recessive manner and presence of disease in two generations is due to pseudodominance.