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Hum Mutat. 2017 Oct;38(10):1355-1359. doi: 10.1002/humu.23274. Epub 2017 Jun 19.

A RAB27A duplication in several cases of Griscelli syndrome type 2: An explanation for cases lacking a genetic diagnosis.

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Centre d'Etudes des Déficits Immunitaires, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France.
INSERM UMR1163, Laboratory of Normal and Pathological Homeostasis of the Immune System, Paris, France.
Paris Descartes University-Sorbonne Paris Cité, Imagine Institute, Paris, France.
Allergy and Immunology Section, Children Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
Department of Pediatric, Allergy and Immunology Section, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Department of Pediatric Immunology, Hematology, and Rheumatology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
INSERM UMR1163, Laboratory of Human Genetics of Infectious Diseases, Paris, France.
Plateforme de Génomique, Fondation IMAGINE, Paris, France.
Plateforme de Bioinformatique, Université Paris Descartes, Paris, France.


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.


Griscelli syndrome; RAB27A; founder effect; gene duplication

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