Genetic Spectrum of Uncombable Hair Syndrome Described
Pathogenic variants discovered in
By Dermsquared Editorial Team | August 31, 2022
In a study published online Aug. 31 in JAMA Dermatology , the authors expand the genotypic spectrum of uncombable hair syndrome (UHS) and identify pathogenic variants in PADI3 , TCHH , and TGM3.
F. Buket Basmanav, Ph.D., from the University of Bonn in Germany, and colleagues examined the genetic spectrum of UHS in a cohort study including 107 unrelated index patients with a suspected diagnosis of UHS and their family members who were recruited worldwide from January 2013 to December 2021.
The researchers found that in 80 of 107 index patients (74.8 percent) who carried biallelic pathogenic variants in PADI3 , TGM3 , or TCHH (i.e., genes that encode functionally related hair shaft proteins), the genetic characteristics were established. The molecular genetic findings from 11 of these patients have already been published. The UHS phenotype was associated with pathogenic variants in PADI3 in 76 patients (71.0 percent). Of the 152 variant PADI3 alleles, 73 and 57 (48.0 and 37.5 percent) were accounted for by the two most commonly observed variants. Two individuals harbored variants in TGM3 , and pathogenic variants in TCHH were seen in two others. A founder effect was suggested in haplotype analyses for the four most commonly observed pathogenic variants in the PADI3 gene.
"This cohort study extends and gives an overview of the genetic variant spectrum of UHS based on molecular genetic analyses of the largest worldwide collective of affected individuals, to our knowledge," the authors write. "Formerly, a diagnosis of UHS could only be made by physical examination of the patient and confirmed by microscopical examination of the hair shaft. The discovery of pathogenic variants in PADI3 , TCHH , and TGM3 may open a new avenue for clinicians and affected individuals by introducing molecular diagnostics for UHS."
One author disclosed financial ties to the pharmaceutical industry.