Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population.

ARCI autosomal recessive congenital ichthyosis congenital ichthyosiform erythroderma epidemiology lamellar ichthyosis

Journal

Experimental dermatology
ISSN: 1600-0625
Titre abrégé: Exp Dermatol
Pays: Denmark
ID NLM: 9301549

Informations de publication

Date de publication:
09 2021
Historique:
revised: 04 03 2021
received: 29 12 2020
accepted: 26 03 2021
pubmed: 1 4 2021
medline: 29 3 2022
entrez: 31 3 2021
Statut: ppublish

Résumé

Autosomal recessive congenital ichthyosis (ARCI) is a rare and heterogeneous skin cornification disorder presenting with generalized scaling and varying degrees of erythema. Clinical manifestations range from lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE) through the most severe form of ARCI, Harlequin ichthyosis (HI). We used homozygosity mapping, whole-exome and direct sequencing to delineate the relative distribution of pathogenic variants as well as identify genotype-phenotype correlations in a cohort of 62 Middle Eastern families with ARCI of various ethnic backgrounds. Pathogenic variants were identified in most ARCI-associated genes including TGM1 (21%), CYP4F22 (18%), ALOX12B (14%), ABCA12 (10%), ALOXE3 (6%), NIPAL4 (5%), PNPLA1 (3%), LIPN (2%) and SDR9C7 (2%). In 19% of cases, no mutation was identified. Our cohort revealed a higher prevalence of CYP4F22 and ABCA12 pathogenic variants and a lower prevalence of TGM1 and NIPAL4 variants, as compared to data obtained in other regions of the world. Most variants (89%) in ALOX12B were associated with CIE and were the most common cause of ARCI among patients of Muslim origin (26%). Palmoplantar keratoderma associated with fissures was exclusively a result of pathogenic variants in TGM1. To our knowledge, this is the largest cohort study of ARCI in the Middle-Eastern population reported to date. Our data demonstrate the importance of population-tailored mutation screening strategies and shed light upon specific genotype-phenotype correlations.

Identifiants

pubmed: 33786896
doi: 10.1111/exd.14345
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1290-1297

Informations de copyright

© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Auteurs

Janan Mohamad (J)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Liat Samuelov (L)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Natalia Malchin (N)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Tom Rabinowitz (T)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Sari Assaf (S)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Liron Malki (L)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Kiril Malovitski (K)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Shirli Israeli (S)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Meital Grafi-Cohen (M)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Ora Bitterman-Deutsch (O)

Dermatology Clinic, Galilee Medical Center, Nahariya, Israel.

Vered Molho-Pessach (V)

Pediatric Dermatology Service, Department of Dermatology, The Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.

Eran Cohen-Barak (E)

Department of Dermatology, Haemek Medical Center, Afula, Israel.
Bruce and Ruth Rappaprt Faculty of Medicine, Technion, Haifa, Israel.

Gideon Bach (G)

Department of Human Genetics, Hadassah Hebrew University Hospital, Jerusalem, Israel.

Ben Zion Garty (BZ)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Schneider Childrens Medical Center, Petah Tikva, Israel.

Reuven Bergman (R)

Department of Dermatology, Rambam Medical Center, Haifa, Israel.

Avikam Harel (A)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Arti Nanda (A)

As'ad Al-Hamad Dermatology Center, Al-Sabah Hospital, Surra, Kuwait.

Giles G Lestringant (GG)

Consultant Dermatologist (ret), British Ministry of Defense, London, UK.

John McGrath (J)

St. John's Institute of Dermatology, King's College London, London, UK.

Stavit Shalev (S)

Bruce and Ruth Rappaprt Faculty of Medicine, Technion, Haifa, Israel.
Institute of Human Genetics, Haemek Medical Center, Afula, Israel.

Noam Shomron (N)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Jacob Mashiah (J)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Marina Eskin-Schwartz (M)

Genetics Institute at Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Eli Sprecher (E)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Ofer Sarig (O)

Division of Dermatology and Pediatric Dermatology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

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