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Autosomal Recessive Congenital Ichthyosis: Genomic Landscape and Phenotypic Spectrum in a Cohort of 125 Consanguineous Families Publisher Pubmed



Youssefian L1, 2, 3 ; Vahidnezhad H1, 4 ; Saeidian AH1, 3 ; Touati A1, 5 ; Sotoudeh S6 ; Mahmoudi H7 ; Mansouri P8 ; Daneshpazhooh M7 ; Aghazadeh N7 ; Hesari KK9 ; Basiri M10 ; Londin E11 ; Kumar G12 ; Zeinali S4, 13 Show All Authors
Authors
  1. Youssefian L1, 2, 3
  2. Vahidnezhad H1, 4
  3. Saeidian AH1, 3
  4. Touati A1, 5
  5. Sotoudeh S6
  6. Mahmoudi H7
  7. Mansouri P8
  8. Daneshpazhooh M7
  9. Aghazadeh N7
  10. Hesari KK9
  11. Basiri M10
  12. Londin E11
  13. Kumar G12
  14. Zeinali S4, 13
  15. Fortina P12, 14
  16. Uitto J1, 15
Show Affiliations
Authors Affiliations
  1. 1. Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, United States
  2. 2. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Genetics, Genomics and Cancer Biology PhD Program, Thomas Jefferson University, Philadelphia, PA, United States
  4. 4. Biotechnology Research Center, Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran
  5. 5. Drexel University College of Medicine, Philadelphia, PA, United States
  6. 6. Department of Dermatology, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Pathology Department, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Sciences, Yazd, Iran
  11. 11. Computational Medicine Center, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States
  12. 12. Sidney Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, United States
  13. 13. Kawsar Human Genetics Research Center, Tehran, Iran
  14. 14. Department of Molecular Medicine, Sapienza University, Rome, Italy
  15. 15. Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, United States

Source: Human Mutation Published:2019


Abstract

Autosomal recessive congenital ichthyosis (ARCI), a phenotypically heterogeneous group of non-syndromic Mendelian disorders of keratinization, is caused by mutations in as many as 13 distinct genes. We examined a cohort of 125 consanguineous families with ARCI for underlying genetic mutations. The patients’ DNA was analyzed with a gene-targeted next generation sequencing panel comprising 38 ichthyosis associated genes. The interpretations of results of genomic data were assisted by genome-wide homozygosity mapping and transcriptome sequencing. Sequence data analysis identified biallelic mutations in 106 families out of a total of 125 (85%), most of them (102, 96.2%) being homozygous, reflecting consanguinity in these families. Among the 85 distinct mutations in 10 different genes, 45 (53%) were previously unreported. Phenotype-genotype correlations allowed assignment of specific genes in the majority of the families to a specific subtype of ARCI, lamellar ichthyosis (LI) versus congenital ichthyosiform erythroderma (CIE). Interestingly, mutations in several genes could give rise to an overlapping phenotype consistent with either LI or CIE. Also, this is the third report for SDR9C7 and SULT2B1, and fourth report for CERS3 mutations. Direct comparison of our results with previously published regional cohorts highlights the global mutation landscape of ARCI, however, population specific differences were noted. © 2018 Wiley Periodicals, Inc.
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