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Molecular Findings and Clinical Manifestations of 18 Iranian Children With Griscelli Syndrome Type 2: Two Novel Homozygote Mutations in Rab27a Gene in a Patient Publisher Pubmed



Tajik S1, 2 ; Badalzadeh M1, 2 ; Houshmand M3 ; Alizadeh Z1, 2 ; Moradi L1, 2 ; Hamidieh AA2, 4 ; Shafiei A5 ; Heris JA6 ; Bahram S7, 8 ; Molitor A7, 8 ; Carapito R7, 8 ; Moin M1, 2 ; Fazlollahi MR1, 2 ; Pourpak Z1, 2
Authors
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Authors Affiliations
  1. 1. Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
  4. 4. Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Allergy and Clinical Immunology division, Pediatric Department, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Allergy and Clinical Immunology, Pediatric Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
  7. 7. Laboratoire d'ImmunoRhumatologie Moleculaire, plateforme GENOMAX, INSERM UMR_S 1109, Faculte de Medecine, Federation Hospitalo-Universitaire OMICARE, Federation de Medecine Translationnelle de Strasbourg (FMTS), LabEx TRANSPLANTEX, Universite de Strasbourg, Strasbourg, France
  8. 8. Service d'Immunologie Biologique, Plateau Technique de Biologie, Pole de Biologie, Nouvel Hopital Civil, 1 place de l'Hopital, Strasbourg, 67091, France

Source: Scandinavian Journal of Immunology Published:2023


Abstract

Griscelli syndrome type 2 (GS2) is an autosomal recessive immunodeficiency characterized by hair hypopigmentation, recurrent fever, hepatosplenomegaly and pancytopenia. This study aims to find new genetic changes and clinical features in 18 children with GS2 caused by the RAB27A gene defect. In all, 18 Iranian children with GS2 who presented with silver grey hair and frequent pyogenic infection were included in this study. After recording demographic and clinical data, PCR sequencing of the RAB27A gene was performed for all exons and exon–intron boundaries. Two patients in this study were subjected to whole-exome sequencing followed by Sanger sequencing. Light microscopy study of hair showed large irregular clumps of pigment with the absence of giant granules on the blood smear. Mutation analysis of the RAB27A gene identified two novel missense mutations as homozygous in a patient, one in exon 2, c.140G>C and another in exon 4, c.328G>T. In addition, for 17 other patients, 6 reported mutations were obtained including c.514_518delCAAGC, c.150_151delAGinsC, c.400_401delAA, c.340delA, c.428T>C and c.221A>G. The mutation c.514_518delCAAGC was the most frequent and found in 10 patients; this mutation may be considered a hotspot in Iran. Early diagnosis and treatment of RAB27A deficiency can contribute to better disease outcomes. In affected families, genetic results could be urgently needed to make a timely decision about haematopoietic stem cell transplantation and prenatal diagnosis. © 2023 The Scandinavian Foundation for Immunology.
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