Griscelli syndrome type 2 (GS2) is a rare and often fatal autosomal recessive, hyperinflammatory disorder. It is associated with hypopigmentation of the skin and the hair, resulting in the characteristic pigment accumulation and clumping in the hair shaft. Loss-of-function mutations in RAB27A, resulting from point mutations, short indel, or large deletions, account for all the cases reported to date. However, several GS2 cases originating from Saudi Arabia lack a genetic diagnosis. Here, we report on a new RAB27A genetic anomaly observed in seven Saudi Arabia families that had remained negative after extensive molecular genomic DNA testing. Linkage analysis and targeted sequencing of the RAB27A genomic region in several of these patients led to the identification of a common homozygous tandem duplication of 38 kb affecting exon 2-5 and resulting in a premature stop codon. The pathogenic effect of this duplication was confirmed by a cDNA analysis and functional assays. The identification of microhomology flanking the breakpoint site suggests a possible underlying mechanism.
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http://dx.doi.org/10.1002/humu.23274 | DOI Listing |
Pediatr Pulmonol
December 2024
Department of Pediatrics and Adolescents Medicine, AUH, Danish Center of Pediatric Pulmonology and Allergology, Aarhus, Denmark.
J Clin Immunol
November 2024
Paediatric Immunology Department, Great Ormond Street Hospital for Children National Health Service (NHS) Foundation Trust, London, UK.
Griscelli syndrome type 2 (GS2) is a rare, life-threatening immunodysregulatory disorder characterised by impaired cytotoxic activity leading to susceptibility to haemophagocytic lymphohistiocytosis (HLH) and hypopigmentation. We completed a literature review and analysis of clinical data of 149 patients with GS2 including 8 new patients.We identified three founder mutations which show diverse phenotypic profiles (RAB27A c.
View Article and Find Full Text PDFPediatr Allergy Immunol
November 2024
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Turk J Biol
July 2024
Department of Stem Cell Sciences, Center for Stem Cell Research and Development, Graduate School of Health Sciences, Hacettepe University, Ankara, Turkiye.
Background/aim: Griscelli Syndrome Type 2 (GS-2) is a rare, inherited immune deficiency caused by a mutation in the gene. The current treatment consists of hematopoietic stem cell transplantation, but a lack of suitable donors warrants the development of alternative treatment strategies, including gene therapy. The development of mutation-specific clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 gene editing technology has opened the way for custom-designed gene correction of patient-derived stem cells.
View Article and Find Full Text PDFBr J Dermatol
October 2024
Department of Dermatology and Venereology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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