Novel 47.5-kb deletion in RAB27A results in severe Griscelli Syndrome Type 2.
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.
Vincent
Lisa M
LM
Section on Human Biochemical Genetics, Medical Genetics Branch, NHGRI, NIH, Bethesda, MD 20892, USA.
Gilbert
Fred
F
DiPace
Jennifer I
JI
Ciccone
Carla
C
Markello
Thomas C
TC
Jeong
Andrew
A
Dorward
Heidi
H
Westbroek
Wendy
W
Gahl
William A
WA
Bussel
James B
JB
Huizing
Marjan
M
D001483:Base Sequence; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D051359:Lymphohistiocytosis, Hemophagocytic; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016116:Piebaldism / Q000235:genetics; D000081207:Primary Immunodeficiency Diseases; D017384:Sequence Deletion / Q000235:genetics*; D020691:rab GTP-Binding Proteins / Q000235:genetics*; D000075745:rab27 GTP-Binding Proteins
D000075745:rab27 GTP-Binding Proteins; C066694:RAB27A protein, human; D020691:rab GTP-Binding Proteins