A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families.
Adolescent
Child
Child, Preschool
Exome
Family Health
Female
Founder Effect
Homozygote
Humans
Infant
Lymphohistiocytosis, Hemophagocytic
/ genetics
Male
Pedigree
Phenotype
Piebaldism
/ genetics
Primary Immunodeficiency Diseases
/ genetics
Qatar
Recurrence
Young Adult
rab27 GTP-Binding Proteins
/ genetics
GS2
HLH
Qatari
RAB27A
founder effect
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
19
05
2020
revised:
13
07
2020
accepted:
21
07
2020
pubmed:
29
8
2020
medline:
16
6
2021
entrez:
29
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32856792
doi: 10.1002/ajmg.a.61829
doi:
Substances chimiques
rab27 GTP-Binding Proteins
0
RAB27A protein, human
EC 3.6.1.-.
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2570-2580Informations de copyright
© 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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