Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations

Meeths, Marie, Bryceson, Yenan T., Rudd, Eva, Zheng, Chengyun, Wood, Stephanie M., Ramme, Kim, Beutel, Karin, Hasle, Henrik, Heilmann, Carsten, Hultenby, Kjell, Ljunggren, Hans-Gustaf, Fadeel, Bengt, Nordenskjold, Magnus and Henter, Jan-Inge (2010) Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations. Pediatric Blood and Cancer, 54 4: 563-572. doi:10.1002/pbc.22357

Author Meeths, Marie
Bryceson, Yenan T.
Rudd, Eva
Zheng, Chengyun
Wood, Stephanie M.
Ramme, Kim
Beutel, Karin
Hasle, Henrik
Heilmann, Carsten
Hultenby, Kjell
Ljunggren, Hans-Gustaf
Fadeel, Bengt
Nordenskjold, Magnus
Henter, Jan-Inge
Title Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations
Journal name Pediatric Blood and Cancer   Check publisher's open access policy
ISSN 1545-5009
Publication date 2010-04-01
Year available 2009
Sub-type Article (original research)
DOI 10.1002/pbc.22357
Volume 54
Issue 4
Start page 563
End page 572
Total pages 10
Place of publication Hoboken, NJ, U.S.A.
Language eng
Formatted abstract
Background. Griscelli syndrome type 2 (GS2) is an autosomalrecessive immunodeficiency caused by mutations in RAB27A, clinically characterized by partial albinism and haemophagocytic lymphohistocytosis (HLH). We evaluated the frequency of RAB27A mutations in 21 unrelated patients with haemophagocytic syndromes without mutations in familial HLH (FHL) causing genes or an established diagnosis of GS2. In addition, we report three patients with known GS2. Moreover, neurological involvement and RAB27A mutations in previously published patients with genetically verified GS2 are reviewed. Procedure. Mutation analysis of RAB27A was performed by direct DNA sequencing. NK cell activity was evaluated and microscopy of the hair was performed to confirm the diagnosis. Results. RAB27A mutations were found in 1 of the 21 families. This Swedish family had three affected children with heterozygous compound mutations consisting of a novel splice error mutation,[c.239G>C], and a nonsense mutation, [c.550C>T], p.R184X. The three additional children all carried homozygous RAB27A mutations, one of which is a novel splice error mutation, [c.240-2A>C]. Of note, five of the six patients displayed neurological symptoms, while three out of six patients displayed NK cell activity within normal reference values, albeit low. A literature review revealed that 67% of GS2 patients have been reported with neurological manifestations. Conclusions. Identification of RAB27A mutations can facilitate prompt diagnosis and treatment, and aid genetic counselling and prenatal diagnosis. Since five of six patients studied herein initially were diagnosed as having FHL, we conclude that the diagnosis of GS2 may be overlooked, particularly in fair-haired patients with haemophagocytic syndromes.
© 2009 Wiley-Liss, Inc.
Keyword Albinism
Griscelli syndrome type 2
Haemophagocytic lymphohistiocytosis
Haemophagocytic syndrome
Familial hemophagocytic lymphohistiocytosis
Stem-cell transplantation
Partial albinism
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 1 December 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
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Created: Sun, 21 Mar 2010, 10:01:42 EST