title: A family with Hoyeraal-Hreidarsson syndrome and four variants in two genes of the telomerase core complex.
abstract: We describe an African American family with Hoyeraal-Hreidarrson syndrome (HHS) in which 2 TERT mutations (causing P530L and A880T amino acid changes) and two in the DKC1 variants (G486R and A487A) were segregating. Both genes are associated with dyskeratosis congenita and HHS. It was important to determine the importance of these mutations in disease pathogenesis to counsel family members. From genetic analysis of family members, telomere length and X-inactivation studies we concluded that compound heterozygosity for the TERT mutations was the major cause of HHS and the DKC1 G486R variant is a rare African variant unlikely to cause disease.
authors: Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, PA 19104, USA.
authors: Paraskevi
authors: P
authors: Vogiatzi
authors: Nieves
authors: N
authors: Perdigones
authors: Philip J
authors: PJ
authors: Mason
authors: David B
authors: DB
authors: Wilson
authors: Monica
authors: M
authors: Bessler
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D019871:Dyskeratosis Congenita / Q000235:genetics*; D005190:Family; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D005434:Flow Cytometry; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D019098:Telomerase / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; D009687:Nuclear Proteins; C509186:TERT protein, human; D019098:Telomerase