title: 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.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, NHGRI, NIH, Bethesda, MD 20892, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Vincent
authors.forename: Fred
authors.initials: F
authors.lastname: Gilbert
authors.forename: Jennifer I
authors.initials: JI
authors.lastname: DiPace
authors.forename: Carla
authors.initials: C
authors.lastname: Ciccone
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Markello
authors.forename: Andrew
authors.initials: A
authors.lastname: Jeong
authors.forename: Heidi
authors.initials: H
authors.lastname: Dorward
authors.forename: Wendy
authors.initials: W
authors.lastname: Westbroek
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
mesh_terms: 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
chemical_list: D000075745:rab27 GTP-Binding Proteins; C066694:RAB27A protein, human; D020691:rab GTP-Binding Proteins