Pathogenic variants identified in individuals with uncombable hair syndrome in JAMA study

The main highlights of this study were:

1. Genetic characterization of UHS patients was determined in 80 (74.8%) of 107 index patients (82 [76.6%] female) who harbor biallelic pathogenic variants in PADI3, TGM3, or TCHH. Her molecular genetic findings for 11 of these 80 have already been published.

2. In 76 (71.0%) individuals, the UHS phenotype was associated with a PADI3 pathogenic variant.

3. The two most commonly observed her PADI3 variants account for 73 (48.0%) and 57 (37.5%), respectively, of a total of 152 her PADI3 variant alleles.

4. Two had a pathogenic variant in TGM3 and the other two had a pathogenic variant in TCHH.

5. Haplotype analysis showed founder effects of the four most frequently observed pathogenic variants in the PADI3 gene.

This cohort study expanded the UHS pathogen variant spectrum and establish that PADI3 was most commonly associated with this rare hair phenotype. Our current results also indicate that the four most commonly observed pathogenic PADI3 variants are much more likely to have descended from their respective common ancestors than to have independently occurred multiple times.

Reference: 

Basmanav, F. B., Cesarato, N., Kumar, S., Borisov, O., Kokordelis, P., Ralser, D. J., Wehner, M., Axt, D., Xiong, X., Thiele, H., Dolgin, V., Gossmann, Y., Fricker, N., Addor, M.-C., … Betz, R. C. (2022). Assessment of the Genetic Spectrum of Uncombable Hair Syndrome in a Cohort of 107 Individuals. In JAMA Dermatology. American Medical Association (AMA). https://doi.org/10.1001/jamadermatol.2022.2319