A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families.

Autor: Al-Sulaiman R; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar.; Department of Adult Hematology/Oncology, Hamad Medical Corporation, Doha, Qatar., Othman A; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar.; Division of Genetic and Genomic Medicine, Sidra Medicine, Doha, Qatar., El-Akouri K; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar.; Division of Genetic and Genomic Medicine, Sidra Medicine, Doha, Qatar., Fareed S; Department of Adult Hematology/Oncology, Hamad Medical Corporation, Doha, Qatar., AlMulla H; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar.; Department of Adult Hematology/Oncology, Hamad Medical Corporation, Doha, Qatar., Sukik A; Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar., Al-Mureikhi M; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar.; Division of Genetic and Genomic Medicine, Sidra Medicine, Doha, Qatar., Shahbeck N; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar.; Division of Genetic and Genomic Medicine, Sidra Medicine, Doha, Qatar., Ali R; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar.; Division of Genetic and Genomic Medicine, Sidra Medicine, Doha, Qatar., Al-Mesaifri F; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar.; Division of Genetic and Genomic Medicine, Sidra Medicine, Doha, Qatar., Musa S; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar., Al-Mulla M; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar.; Division of Genetic and Genomic Medicine, Sidra Medicine, Doha, Qatar., Ibrahim K; Division of Pediatric Neurology, Sidra Medicine, Doha, Qatar., Mohamed K; Division of Pediatric Neurology, Sidra Medicine, Doha, Qatar., Al-Nesef MA; Department of Medicine, Hamad Medical Corporation, Doha, Qatar., Ehlayel M; Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.; Weill Cornell Medical College, Doha, Qatar., Ben-Omran T; Department of Medical Genetics, Hamad Medical Corporation, Doha, Qatar.; Division of Genetic and Genomic Medicine, Sidra Medicine, Doha, Qatar.; Weill Cornell Medical College, Doha, Qatar.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2020 Nov; Vol. 182 (11), pp. 2570-2580. Date of Electronic Publication: 2020 Aug 28.
DOI: 10.1002/ajmg.a.61829
Abstrakt: Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disorder caused by pathogenic variants in the RAB27A gene and characterized by partial albinism, immunodeficiency, and occasional hematological and neurological involvement. We reviewed and analyzed the medical records of 12 individuals with GS2 from six families belonging to a highly consanguineous Qatari tribe and with a recurrent pathogenic variant in the RAB27A gene (NM_004580.4: c.244C > T, p.Arg82Cys). Detailed demographic, clinical, and molecular data were collected. Cutaneous manifestations were the most common presentation (42%), followed by neurological abnormalities (33%) and immunodeficiency (25%). The most severe manifestation was HLH (33%). Among the 12 patients, three patients (25%) underwent HSCT, and four (33%) died. The cause of death in all four patients was deemed HLH, providing evidence for this complication's fatal nature. Interestingly, two affected patients (16%) were asymptomatic. This report highlights the broad spectrum of clinical presentations of GS2 associated with a founder variant in the RAB27A gene (c.244C > T, p.Arg82Cys). Early suspicion of GS2 among Qatari patients with cutaneous manifestations, neurological findings, immunodeficiency, and HLH would shorten the diagnostic odyssey, guide early and appropriate treatment, and prevent fatal outcomes.
(© 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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