Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population
Janan Mohamad, Liat Samuelov, Natalia Malchin, Tom Rabinowitz, Sari Assaf, Liron Malki, Kiril Malovitski, Shirli Israeli, Meital Grafi-Cohen, Ora Bitterman-Deutsch, Vered Molho-Pessach, Eran Cohen-Barak, Gideon Bach, Ben Zion Garty, Reuven Bergman, Avikam Harel, Arti Nanda, Giles G. Lestringant, John McGrath, Stavit Shalev
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Noam Shomron, Jacob Mashiah, Marina Eskin-Schwartz, Eli Sprecher, Ofer Sarig
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.
Experimental Dermatology
https://doi.org/10.1111/exd.14345
autosomal recessive congenital ichthyosis
congenital ichthyosiform erythroderma
lamellar ichthyosis
10.1111/exd.14345
Dive into the research topics of 'Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population'. Together they form a unique fingerprint.
Ichthyosis Medicine & Life Sciences 100%
Molecular Epidemiology Medicine & Life Sciences 83%
Mutation Chemical Compounds 60%
Congenital Ichthyosiform Erythroderma Medicine & Life Sciences 42%
Lamellar Ichthyosis Medicine & Life Sciences 38%
Disorder Chemical Compounds 30%
Genetic Association Studies Medicine & Life Sciences 25%
Mohamad, J., Samuelov, L., Malchin, N., Rabinowitz, T., Assaf, S., Malki, L., Malovitski, K., Israeli, S., Grafi-Cohen, M., Bitterman-Deutsch, O., Molho-Pessach, V., Cohen-Barak, E., Bach, G., Garty, B. Z., Bergman, R., Harel, A., Nanda, A., Lestringant, G. G., McGrath, J., ... Sarig, O. (2021). Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population. Experimental Dermatology, 30(9), 1290-1297. https://doi.org/10.1111/exd.14345
Mohamad, Janan ; Samuelov, Liat ; Malchin, Natalia ; Rabinowitz, Tom ; Assaf, Sari ; Malki, Liron ; Malovitski, Kiril ; Israeli, Shirli ; Grafi-Cohen, Meital ; Bitterman-Deutsch, Ora ; Molho-Pessach, Vered ; Cohen-Barak, Eran ; Bach, Gideon ; Garty, Ben Zion ; Bergman, Reuven ; Harel, Avikam ; Nanda, Arti ; Lestringant, Giles G. ; McGrath, John ; Shalev, Stavit ; Shomron, Noam ; Mashiah, Jacob ; Eskin-Schwartz, Marina ; Sprecher, Eli ; Sarig, Ofer. / Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population. In: Experimental Dermatology. 2021 ; Vol. 30, No. 9. pp. 1290-1297.
@article{88285585f20e4c9693e1b31f59a071bc,
title = "Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population",
abstract = "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.",
keywords = "ARCI, autosomal recessive congenital ichthyosis, congenital ichthyosiform erythroderma, epidemiology, lamellar ichthyosis",
author = "Janan Mohamad and Liat Samuelov and Natalia Malchin and Tom Rabinowitz and Sari Assaf and Liron Malki and Kiril Malovitski and Shirli Israeli and Meital Grafi-Cohen and Ora Bitterman-Deutsch and Vered Molho-Pessach and Eran Cohen-Barak and Gideon Bach and Garty, {Ben Zion} and Reuven Bergman and Avikam Harel and Arti Nanda and Lestringant, {Giles G.} and John McGrath and Stavit Shalev and Noam Shomron and Jacob Mashiah and Marina Eskin-Schwartz and Eli Sprecher and Ofer Sarig",
note = "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: {\textcopyright} 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",
doi = "10.1111/exd.14345",
journal = "Experimental Dermatology",
publisher = "Wiley-Blackwell Publishing Ltd",
Mohamad, J, Samuelov, L, Malchin, N, Rabinowitz, T, Assaf, S, Malki, L, Malovitski, K, Israeli, S, Grafi-Cohen, M, Bitterman-Deutsch, O, Molho-Pessach, V, Cohen-Barak, E, Bach, G, Garty, BZ, Bergman, R, Harel, A, Nanda, A, Lestringant, GG, McGrath, J, Shalev, S, Shomron, N, Mashiah, J, Eskin-Schwartz, M, Sprecher, E & Sarig, O 2021, 'Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population', Experimental Dermatology, vol. 30, no. 9, pp. 1290-1297. https://doi.org/10.1111/exd.14345
Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population. / Mohamad, Janan; Samuelov, Liat; Malchin, Natalia; Rabinowitz, Tom; Assaf, Sari; Malki, Liron; Malovitski, Kiril; Israeli, Shirli; Grafi-Cohen, Meital; Bitterman-Deutsch, Ora; Molho-Pessach, Vered; Cohen-Barak, Eran; Bach, Gideon; Garty, Ben Zion; Bergman, Reuven; Harel, Avikam; Nanda, Arti; Lestringant, Giles G.; McGrath, John; Shalev, Stavit; Shomron, Noam; Mashiah, Jacob; Eskin-Schwartz, Marina; Sprecher, Eli; Sarig, Ofer.
In: Experimental Dermatology, Vol. 30, No. 9, 01.09.2021, p. 1290-1297.
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
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
U2 - 10.1111/exd.14345
DO - 10.1111/exd.14345
JO - Experimental Dermatology
JF - Experimental Dermatology
Mohamad J, Samuelov L, Malchin N, Rabinowitz T, Assaf S, Malki L et al. Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population. Experimental Dermatology. 2021 Sep 1;30(9):1290-1297. https://doi.org/10.1111/exd.14345