Molecular epidemiology of pachyonychia congenita in the Israeli population.
Journal
Clinical and experimental dermatology
ISSN: 1365-2230
Titre abrégé: Clin Exp Dermatol
Pays: England
ID NLM: 7606847
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
accepted:
10
11
2020
pubmed:
16
11
2020
medline:
16
11
2021
entrez:
15
11
2020
Statut:
ppublish
Résumé
Pachyonychia congenita (PC) is a rare autosomal dominant disorder featuring palmoplantar keratoderma, nail dystrophy, oral leucokeratosis, pilosebaceous cysts and natal teeth. PC results from dominant mutations in one of five genes (KRT6A, KRT6B, KRT6C, KRT16, KRT17) encoding keratin proteins. To delineate the clinical and genetic features of PC in a series of Israeli patients. We used direct sequencing of genomic DNA, and also used cDNA sequencing where applicable. We collected clinical information and molecular data in a cohort of Israeli families diagnosed with PC (n = 16). Most of the patients were Ashkenazi Jews and had a family history of PC. The most common clinical findings were painful focal plantar keratoderma (94%) accompanied by nail dystrophy (81%), pilosebaceous cysts (31%) and prenatal/natal teeth (13%). In contrast to the high prevalence of KRT6A mutations in other populations, we found that KRT16 mutations were the most common type among Israeli patients with PC (56%). Most (77%) of the Israeli patients with PC with KRT16 mutation carried the same variant (c.380G>A; p.R127H) and shared the same haplotype around the KRT16 locus, suggestive of a founder effect. The data gleaned from this study emphasizes the importance of population-specific tailored diagnostic strategies.
Sections du résumé
BACKGROUND
BACKGROUND
Pachyonychia congenita (PC) is a rare autosomal dominant disorder featuring palmoplantar keratoderma, nail dystrophy, oral leucokeratosis, pilosebaceous cysts and natal teeth. PC results from dominant mutations in one of five genes (KRT6A, KRT6B, KRT6C, KRT16, KRT17) encoding keratin proteins.
AIM
OBJECTIVE
To delineate the clinical and genetic features of PC in a series of Israeli patients.
METHODS
METHODS
We used direct sequencing of genomic DNA, and also used cDNA sequencing where applicable.
RESULTS
RESULTS
We collected clinical information and molecular data in a cohort of Israeli families diagnosed with PC (n = 16). Most of the patients were Ashkenazi Jews and had a family history of PC. The most common clinical findings were painful focal plantar keratoderma (94%) accompanied by nail dystrophy (81%), pilosebaceous cysts (31%) and prenatal/natal teeth (13%). In contrast to the high prevalence of KRT6A mutations in other populations, we found that KRT16 mutations were the most common type among Israeli patients with PC (56%). Most (77%) of the Israeli patients with PC with KRT16 mutation carried the same variant (c.380G>A; p.R127H) and shared the same haplotype around the KRT16 locus, suggestive of a founder effect.
CONCLUSION
CONCLUSIONS
The data gleaned from this study emphasizes the importance of population-specific tailored diagnostic strategies.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
663-668Informations de copyright
© 2020 British Association of Dermatologists.
Références
Bowden PE, Haley JL, Kansky A et al. Mutation of a type II keratin gene (K6a) in pachyonychia congenita. Nat Genet 1995; 10: 363-5.
McLean WH, Rugg EL, Lunny DP et al. Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet 1995; 9: 273-8.
Smith FJ, Jonkman MF, van Goor H et al. A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2. Hum Mol Genet 1998; 7: 1143-8.
Wilson NJ, Messenger AG, Leachman SA et al. Keratin K6c mutations cause focal palmoplantar keratoderma. J Invest Dermatol 2010; 130: 425-9.
Leachman SA, Kaspar RL, Fleckman P et al. Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10: 3-17.
Liao H, Sayers JM, Wilson NJ et al. A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita. J Dermatol Sci 2007; 48: 199-205.
Eliason MJ, Leachman SA, Feng BJ et al. A review of the clinical phenotype of 254 patients with genetically confirmed pachyonychia congenita. J Am Acad Dermatol 2012; 67: 680-6.
McLean WH, Hansen CD, Eliason MJ, Smith FJ. The phenotypic and molecular genetic features of pachyonychia congenita. J Invest Dermatol 2011; 131: 1015-17.
Israeli S, Goldberg I, Fuchs-Telem D et al. Non-syndromic autosomal recessive congenital ichthyosis in the Israeli population. Clin Exp Dermatol 2013; 38: 911-16.
Abu Sa'd J, Indelman M, Pfendner E et al. Molecular epidemiology of hereditary epidermolysis bullosa in a Middle Eastern population. J Invest Dermatol 2006; 126: 777-81.
Mizrachi-Koren M, Shemer S, Morgan M et al. Homozygosity mapping as a screening tool for the molecular diagnosis of hereditary skin diseases in consanguineous populations. J Am Acad Dermatol 2006; 55: 393-401.
Zlotogora J, van Baal S, Patrinos GP. Documentation of inherited disorders and mutation frequencies in the different religious communities in Israel in the Israeli National Genetic Database. Hum Mutat 2007; 28: 944-9.
Ciubotaru D, Bergman R, Baty D et al. Epidermolysis bullosa simplex in Israel: clinical and genetic features. Arch Dermatol 2003; 139: 498-505.
Wilson NJ, O'Toole EA, Milstone LM et al. The molecular genetic analysis of the expanding pachyonychia congenita case collection. Br J Dermatol 2014; 171: 343-55.
Du ZF, Xu CM, Zhao Y et al. Two novel de novo mutations of KRT6A and KRT16 genes in two Chinese pachyonychia congenita pedigrees with fissured tongue or diffuse plantar keratoderma. Eur J Dermatol 2012; 22: 476-80.
Gutierrez JA, Hannoush ZC, Vargas LG et al. A novel non-sense mutation in keratin 10 causes a familial case of recessive epidermolytic ichthyosis. Mol Genet Genomic Med 2013; 1: 108-12.
Terron-Kwiatkowski A, van Steensel MA, van Geel M et al. Mutation S233L in the 1B domain of keratin 1 causes epidermolytic palmoplantar keratoderma with "tonotubular" keratin. J Invest Dermatol 2006; 126: 607-13.
Samuelov L, Smith FJD, Hansen CD, Sprecher E. Revisiting pachyonychia congenita: a case-cohort study of 815 patients. Br J Dermatol 2020; 182: 738-46.
Israeli S, Sarig O, Garty B et al. Molecular analysis of a series of Israeli families with Comel-Netherton syndrome. Dermatology 2014; 228: 183-8.
Koren A, Sprecher E, Reider E, Artzi O. A treatment protocol for botulinum toxin injections in the treatment of pachyonychia congenita-associated keratoderma. Br J Dermatol 2020; 182: 671-7.
Lin MT, Levy ML, Bowden P et al. Identification of sporadic mutations in the helix initiation motif of keratin 6 in two pachyonychia congenita patients: further evidence for a mutational hot spot. Exp Dermatol 1999; 8: 115-19.
Shamsher MK, Navsaria HA, Stevens HP et al. Novel mutations in keratin 16 gene underly focal non-epidermolytic palmoplantar keratoderma (NEPPK) in two families. Hum Mol Genet 1995; 4: 1875-81.
Covello SP, Smith FJ, Sillevis Smitt JH et al. Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2. Br J Dermatol 1998; 139: 475-80.
Smith FJ, Corden LD, Rugg EL et al. Missense mutations in keratin 17 cause either pachyonychia congenita type 2 or a phenotype resembling steatocystoma multiplex. J Invest Dermatol 1997; 108: 220-3.
Smith FJ, Liao H, Cassidy AJ et al. The genetic basis of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10: 21-30.