TY - JOUR
T1 - Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population
AU - Mohamad, Janan
AU - Samuelov, Liat
AU - Malchin, Natalia
AU - Rabinowitz, Tom
AU - Assaf, Sari
AU - Malki, Liron
AU - Malovitski, Kiril
AU - Israeli, Shirli
AU - Grafi-Cohen, Meital
AU - Bitterman-Deutsch, Ora
AU - Molho-Pessach, Vered
AU - Cohen-Barak, Eran
AU - Bach, Gideon
AU - Garty, Ben Zion
AU - Bergman, Reuven
AU - Harel, Avikam
AU - Nanda, Arti
AU - Lestringant, Giles G.
AU - McGrath, John
AU - Shalev, Stavit
AU - Shomron, Noam
AU - Mashiah, Jacob
AU - Eskin-Schwartz, Marina
AU - Sprecher, Eli
AU - Sarig, Ofer
N1 - Funding Information:
We want to acknowledge the patients and patients? families for their kind contribution and to the Ram family who finance generously this study.
Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
KW - ARCI
KW - autosomal recessive congenital ichthyosis
KW - congenital ichthyosiform erythroderma
KW - epidemiology
KW - lamellar ichthyosis
UR - http://www.scopus.com/inward/record.url?scp=85104301749&partnerID=8YFLogxK
U2 - 10.1111/exd.14345
DO - 10.1111/exd.14345
M3 - Article
C2 - 33786896
AN - SCOPUS:85104301749
SN - 0906-6705
VL - 30
SP - 1290
EP - 1297
JO - Experimental Dermatology
JF - Experimental Dermatology
IS - 9
ER -