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Genotype–phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis

Lookup NU author(s): Dr Suzy Leech


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© 2019 British Association of Dermatologists. Background: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype–phenotype correlation in some populations. Objectives: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype–phenotype correlation. Methods: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. Results: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. Conclusions: These data refine genotype–phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management.

Publication metadata

Author(s): Simpson JK, Martinez-Queipo M, Onoufriadis A, Tso S, Glass E, Liu L, Higashino T, Scott W, Tierney C, Simpson MA, Desomchoke R, Youssefian L, SaeIdian AH, Vahidnezhad H, Bisquera A, Ravenscroft J, Moss C, O'Toole EA, Burrows N, Leech S, Jones EA, Lim D, Ilchyshyn A, Goldstraw N, Cork MJ, Darne S, Uitto J, Martinez AE, Mellerio JE, McGrath JA

Publication type: Article

Publication status: Published

Journal: British Journal of Dermatology

Year: 2020

Volume: 182

Issue: 3

Pages: 729-737

Print publication date: 01/03/2020

Online publication date: 26/08/2019

Acceptance date: 31/05/2019

ISSN (print): 0007-0963

ISSN (electronic): 1365-2133

Publisher: Wiley-Blackwell Publishing Ltd


DOI: 10.1111/bjd.18211

PubMed id: 31168818


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