title: Novel mutation in two brothers with Hermansky Pudlak syndrome type 3.
abstract: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder causing oculocutaneous albinism, bleeding disorder and ceroid lipofuscinosis. Platelets from HPS patients are characterized by impaired secretion of dense (δ)-bodies (CD63). Meanwhile, there are ten known human HPS genes, each leading to a particular clinical HPS subtype (HPS1-HPS10). We report on two Turkish brothers showing typical HPS phenotype comprising oculocutaneous albinism and bleeding symptoms. Pathological bleeding time as well as platelet aggregometry analyses revealed impaired platelet function. The brothers demonstrated absence of platelet δ-granule secretion as measured by flow cytometry. Using molecular genetic analyses, a novel homozygous 1bp-deletion in the HPS3 gene was identified in both brothers. In addition, the younger brother with HPS3 demonstrated psychomotoric retardation and cranial gliosis (magnetic resonance imaging, MRI). Array-CGH analysis revealed a de novo 0.482Mb deletion on chromosome 17 which is not present in his brother and parents. In this study, we identified a novel 1bp-deletion in the HPS3 gene causing HPS3 phenotype in two brothers. In patients with oculocutaneous albinism and increased bleeding symptoms platelet function should be analyzed. The identification of the molecular genetic defect allows the classification to a particular HPS subtype and is important for therapy and prognosis.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Sandrock-Lang
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bartsch
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Buechele
authors.affiliation: MGZ - Medical Genetic Center, Munich, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Koehler
authors.affiliation: Department of Neuroradiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Carl Philipp
authors.initials: CP
authors.lastname: Simon-Gabriel
authors.affiliation: Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eckenweiler
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: barbara.zieger@uniklinik-freiburg.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zieger
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D001792:Blood Platelets / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D010375:Pedigree; D010974:Platelet Aggregation; D017384:Sequence Deletion; D035781:Siblings; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C432680:HPS3 protein, human; D047908:Intracellular Signaling Peptides and Proteins
keywords: Deletion 17q12q21.1; HPS3; Hermansky-Pudlak syndrome; Novel mutation; Psychomotoric retardation