Phenotypic Diversity and Mutation Spectrum in Hypotrichosis with Juvenile Macular Dystrophy

Margarita Indelman, Christian P. Hamel, Reuven Bergman, Ken K. Nischal, Dorothy Thompson, Marie Odile Surget, Michal Ramon, Hatam Ganthos, Benjamin Miller, Gabriele Richard, Rina Leibu, Isabelle Russell-Eggitt, Eli Sprecher*

*Corresponding author for this work

Research output: Contribution to journalLetterpeer-review


Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by abnormal growth of scalp hair during infancy, and by the later occurrence of macular degeneration leading to blindness during the first to third decade of life. Hypotrichosis with juvenile macular dystrophy was recently shown to result from mutations in CDH3 encoding P-cadherin. In this study, we assessed 27 individuals, including nine patients, belonging to five families in an attempt to characterize further the CDH3 mutation spectrum and delineate possible phenotype-genotype correlations. Deleterious biallelic mutations, predicted to lead to the translation of a dysfunctional protein, were found in all affected individuals. Four of these mutations are novel. Affected individuals of two large separate apparently unrelated families of Arab Israeli origin were found to carry the same homozygous mis-sense mutation (R503H) in exon 11 of the CDH3 gene. This mutation, which alters a Ca2+ -binding site in the fourth extracellular domain of P-cadherin, was previously described in a third unrelated Arab Israeli family. Using haplotype analysis for a series of polymorphic markers encompassing the CDH3 gene, we obtained evidence suggesting a founder effect for R503H in the Arab Israeli population. We also compared the dermatologic and ophthalmologic features of 22 hypotrichosis with juvenile macular dystrophy patients with known recessive mutations in CDH3. Whereas hair paucity and macular degeneration were found in all patients, we noticed significant interfamilial and intrafamilial differences in hair morphology, associated skin findings as well as severity and age of onset of visual disability. Altogether, our results obtained in a series of families of various ethnic origins firmly establish mutations in CDH3 as the proximal cause of hypotrichosis with juvenile macular dystrophy and demonstrate genetic homogeneity as well as phenotypic heterogeneity in this disorder.

Original languageEnglish
Pages (from-to)1217-1220
Number of pages4
JournalJournal of Investigative Dermatology
Issue number5
StatePublished - Nov 2003
Externally publishedYes


FundersFunder number
Rambam Medical Center R&D division
Technion Research Fund


    • Atrichia
    • Hair
    • Hypotrichosis
    • Lentigo
    • Macular degeneration
    • Pigmentation
    • Retinal dystrophy


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