Keratin 17-Related Recessive Atypical Pachyonychia Congenita with Variable Hair and Tooth Anomalies

June 2022 in “ European journal of human genetics ”

Mine Koprulu, Muhammad Naeem, Gökhan Nalbant, Rana Muhammad Kamran Shabbir, Tariq Mahmood, Zele Huma, Sajid Malik, Aslıhan Tolun

pachyonychia congenita KRT17 keratin 17 plantar keratoderma folliculitis alopecia sparse eyebrows acanthosis nigricans exome sequencing homozygous mutation heterozygous variants genetic testing Sanger sequencing PC

Studysummary This study reports the first cases of recessive KRT17-related pachyonychia congenita involving all ectodermal derivatives in seven members of two consanguineous Pakistani families. Our plain-language summary of this paper — not a Tressless recommendation.

This document reports the first known case of pachyonychia congenita (PC) affecting all ectodermal derivatives and the first recessive KRT17-related PC, observed in seven members across two consanguineous Pakistani families. The atypical PC is marked by a combination of symptoms including pachyonychia, plantar keratoderma, folliculitis, alopecia, sparse eyebrows, dental anomalies, and variable acanthosis nigricans, among others. Exome sequencing revealed a homozygous KRT17 c.281G>A (p.(Arg94His)) mutation in affected individuals, with linkage mapping supporting a single locus for the disorder. This contrasts with the heterozygous variants of KRT17, which cause PC2 with dominant inheritance and different symptoms. The study also highlights the importance of comprehensive genetic testing, as Sanger sequencing alone showed heterozygosity for the causal variant, suggesting that testing parents for variants found in siblings could reveal recessive inheritance patterns in other KRT genes as well.

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research Homozygous Dominant Missense Mutation in Keratin 17 Leads to Alopecia in Addition to Severe Pachyonychia Congenita

22 citations , February 2012 in “Journal of Investigative Dermatology”

A specific gene mutation causes severe skin and nail issues and hair loss.

research Keratin Disorders: From Gene to Therapy

109 citations , September 2011 in “Human molecular genetics online/Human molecular genetics”

This review discusses keratin disorders and potential RNA interference therapeutics, reporting no new clinical findings but highlighting the promise of siRNA for future treatments.

research Keratin 17 Null Mice Exhibit Age- And Strain-Dependent Alopecia

122 citations , June 2002 in “Genes & Development”

This study found that K17 is crucial for the structural integrity and survival of hair-producing cells, with K17 null mice developing alopecia due to hair fragility and follicular alterations.