Molecular basis of hypotrichosis with juvenile macular dystrophy in two siblings

Background Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse and short scalp hair from birth, followed within a few years by progressive macular degeneration leading to blindness. HJMD was shown to result from mutations in CDH3 encoding P-cadherin. Objectives In the present study, we attempted to identify the molecular basis of abnormal hair growth in two siblings of Arab Muslim origin with hypotrichosis but no visual symptoms. Methods Mutation analysis was performed using direct sequencing and polymerase chain reaction-restriction fragment length polymorphism analysis. Results Patients displayed sparse and short hair since birth. Significant macular degenerative pigmentary changes were noticed in the face of normal visual acuity. Despite the fact that a single CDH3 mutation had previously been described in several families of Israeli Arab Muslim origin, the two affected patients were found to be homozygous carriers of a novel nonsense mutation (Y615X) predicted to result in premature termination of P-cadherin translation. Conclusions The present results indicate that all patients with congenital hypotrichosis should undergo thorough fundus examination, which, when revealing pigmentary macular changes, can be considered as indicative of an underlying CDH3 causative mutation.