Novel 47.5-kb deletion in RAB27A results in severe Griscelli Syndrome Type 2.

Abstract

Griscelli syndrome (GS), a rare autosomal recessive disorder characterized by partial albinism and immunological impairment and/or severe neurological impairment, results from mutations in the MYO5A (GS1), RAB27A (GS2), or MLPH (GS3) genes. We identified a Hispanic patient born of a consanguineous union who presented with immunodeficiency, partial albinism, hepatic dysfunction, hemophagocytosis, neurological impairment, nystagmus, and silvery hair indicative of Griscelli Syndrome Type 2 (GS2). We screened for point mutations, but only exons 2-6 of the patient's DNA could be PCR-amplified. Whole genome analysis using the Illumina 1M-Duo DNA Analysis BeadChip identified a homozygous deletion in the patient's DNA. The exact breakpoints of the 47.5-kb deletion were identified as chr15q15-q21.1: g.53332432_53379990del (NCBI Build 37.1); the patient lacks the promoter and 5'UTR regions of RAB27A, thus confirming the diagnosis of GS2.

• Authors: Lisa M Vincent, Fred Gilbert, Jennifer I DiPace, Carla Ciccone, Thomas C Markello, Andrew Jeong, Heidi Dorward, Wendy Westbroek, William A Gahl, James B Bussel, Marjan Huizing
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 101 Issue 1 Pg. 62-5 (Sep 2010) ISSN: 1096-7206 [Electronic] United States
• PMID: 20591709 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• rab27 GTP-Binding Proteins
• RAB27A protein, human
• rab GTP-Binding Proteins

Topics

• Base Sequence
• Humans
• Immunologic Deficiency Syndromes (genetics)
• Lymphohistiocytosis, Hemophagocytic
• Models, Genetic
• Molecular Sequence Data
• Mutation
• Pedigree
• Piebaldism (genetics)
• Primary Immunodeficiency Diseases
• Sequence Deletion (genetics)
• rab GTP-Binding Proteins (genetics)
• rab27 GTP-Binding Proteins