Mutations in the Desmoglein 1 Gene in Five Pakistani Families with Striate Palmoplantar Keratoderma

Overview

Journal J Dermatol Sci

Publisher Elsevier

Specialty Dermatology

Date 2009 Jan 23

PMID 19157795

Citations 8

Authors

Martha B Dua-Awereh

Yutaka Shimomura

Liv Kraemer

Muhammad Wajid

Angela M Christiano

Affiliations

Soon will be listed here.

Abstract

Background: Striate palmoplantar keratoderma (SPPK; OMIM #148700) is a rare autosomal dominant genodermatosis characterized by linear hyperkeratosis on the digits and hyperkeratosis on the palms and soles. SPPK is known to be caused by heterozygous mutations in either the desmoglein 1 (DSG1), desmoplakin (DSP), or keratin 1 (KRT1) genes.

Objective: To define the molecular basis of SPPK in five Pakistani families showing a clear autosomal dominant inheritance pattern of SPPK.

Methods: Based on previous reports of DSG1 mutations in SPPK, we performed direct sequencing of the DSG1 gene of all five families.

Results: Mutation analysis resulted in the identification of one recurrent mutation (p.R26X) and four novel mutations (c.Ivs4-2A>G, c.515C>T, c.Ivs9-3C>G, and c.1399delA) in the DSG1 gene. Each mutation is predicted to cause haploinsufficiency of DSG1 protein.

Conclusion: The results of our study further underscore the significance of the desmoglein gene family in diseases of epidermal integrity.

Citing Articles

Striate palmoplantar keratoderma: a novel DSG1 mutation, combined with an LDLR mutation.

He L, Zhu G Genes Genomics. 2024; 47(1):1-10.

PMID: 39503931 DOI: 10.1007/s13258-024-01587-7.

Novel nonsense variants in SLURP1 and DSG1 cause palmoplantar keratoderma in Pakistani families.

Akbar A, Prince C, Payne C, Fasham J, Ahmad W, Baple E BMC Med Genet. 2019; 20(1):145.

PMID: 31443639 PMC: 6708247. DOI: 10.1186/s12881-019-0872-1.

Mutations in desmoglein 1 cause diverse inherited palmoplantar keratoderma phenotypes: implications for genetic screening.

Lovgren M, McAleer M, Irvine A, Wilson N, Tavadia S, Schwartz M Br J Dermatol. 2016; 176(5):1345-1350.

PMID: 27534273 PMC: 5485079. DOI: 10.1111/bjd.14973.

Interpretation of mRNA splicing mutations in genetic disease: review of the literature and guidelines for information-theoretical analysis.

Caminsky N, Mucaki E, Rogan P F1000Res. 2015; 3:282.

PMID: 25717368 PMC: 4329672. DOI: 10.12688/f1000research.5654.1.

A spontaneous deletion within the desmoglein 3 extracellular domain of mice results in hypomorphic protein expression, immunodeficiency, and a wasting disease phenotype.

Kountikov E, Poe J, Maclver N, Rathmell J, Tedder T Am J Pathol. 2014; 185(3):617-30.

PMID: 25542773 PMC: 4348474. DOI: 10.1016/j.ajpath.2014.10.025.

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