Background: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse and short hair, heralding progressive degeneration of the retinal pigment epithelium, which leads to blindness by the second decade of life. The disorder is caused by mutations in CDH3, a gene encoding P-cadherin, a major component of adherens junctions. Most HJMD cases reported to date have been shown to be caused by homozygous CDH3 mutations segregating in consanguineous families.
Aim and methods: To elucidate the genetic basis of HJMD in two nonconsanguineous families, we established the coding sequence of CDH3 in four patients and their healthy siblings.
Results: The four patients demonstrated markedly variable degrees of visual acuity impairment. Novel biallelic recessive mutations were identified in all affected individuals. One patient in the first family was found to carry two heterozygous mutations, IVS2 + 1G-->A and p.E504K; the other three patients in the second family were compound heterozygous for a missense mutation, p.H575R, and a nonsense mutation, p.R221X.
Conclusion: This paper expands the spectrum of known mutations in CDH3 and points to the existence of clinical heterogeneity in this syndrome.