Molecular findings and clinical manifestations of 18 Iranian children with Griscelli syndrome type 2: Two novel homozygote mutations in RAB27A gene in a patient

Molecular findings and clinical manifestations of 18 Iranian children with Griscelli syndrome type 2: Two novel homozygote mutations in RAB27A gene in a patient

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,...

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Bibliographic Details
Published in:Scandinavian journal of immunology Vol. 97; no. 5; pp. e13264 - n/a
Main Authors: Tajik, Shaghayegh, Badalzadeh, Mohsen, Houshmand, Massoud, Alizadeh, Zahra, Moradi, Leila, Hamidieh, Amir Ali, Shafiei, Alireza, Heris, Javad Ahmadiani, Bahram, Seiamak, Molitor, Anne, Carapito, Raphael, Moin, Mostafa, Fazlollahi, Mohammad Reza, Pourpak, Zahra
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 01-05-2023
Subjects:
Child
Children
Decision making
Exons
Genetics
Griscelli syndrome
Hair
Hematopoietic stem cells
Homozygote
Humans
Immunodeficiency
Iran
Life Sciences
Light microscopy
Missense mutation
Mutation
novel mutation
Pancytopenia
Patients
Pigmentation
Prenatal diagnosis
rab GTP-Binding Proteins - genetics
rab GTP-Binding Proteins - metabolism
rab27 GTP-Binding Proteins - genetics
RAB27A gene
Stem cell transplantation
Iran
novel mutation
Griscelli syndrome
RAB27A gene
genetics, metabolism
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Summary: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.
Bibliography:Correction added on 16 April 2023, after first online publication: the 4th affiliation was updated.
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content type line 23
ISSN:0300-9475
1365-3083
1365-3083
DOI:10.1111/sji.13264