An autosomal recessive form of monilethrix is caused by mutations in DSG4: clinical overlap with localized autosomal recessive hypotrichosis.
Monilethrix is a structural defect of the hair shaft usually inherited in an autosomal dominant fashion and caused by mutations in the hHb1, hHb3, and hHb6 keratin genes. Autosomal recessive inheritance in this disease has been sporadically reported. We encountered 12 Jewish families from Iraq, Iran, and Morocco with microscopic findings of monilethrix, but with no evidence of vertical transmission. Since no mutations were found in these three hair keratin genes, we examined nine chromosomal regions containing gene clusters encoding skin and hair genes. On chromosome 18q, a common haplotype in the homozygous state was found among all seven Iraqi patients, but not in 20 controls (P<0.0001). Sequencing of the main candidate gene from this region revealed four different mutations in desmoglein 4 (DSG4). Mutations in DSG4 have been previously reported in localized autosomal recessive hypotrichosis, a disorder that shares the clinical features of monilethrix but lacks the characteristic microscopic appearance of the hair shaft. Our findings have important implications for genetic counseling to monilethrix patients and families, and suggest that DSG4-associated hair disorders may be more common than previously thought.
Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. zloto@cc.huji.ac.il
Abraham
A
Zlotogorski
Dina
D
Marek
Liran
L
Horev
Almogit
A
Abu
Dan
D
Ben-Amitai
Liora
L
Gerad
Arieh
A
Ingber
Moshe
M
Frydman
Haike
H
Reznik-Wolf
Daniel A
DA
Vardy
Elon
E
Pras
D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D051182:Desmogleins / Q000235:genetics*; D005817:Genetic Counseling; D006197:Hair / Q000473:pathology*; D006201:Hair Diseases / Q000235:genetics* / Q000473:pathology; D006239:Haplotypes; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics* / Q000473:pathology; D018445:Infectious Disease Transmission, Vertical; D009154:Mutation; D010375:Pedigree
C473409:DSG4 protein, human; D051182:Desmogleins