title: Compound heterozygous mutations of the SBDS gene in a patient with Shwachman-Diamond syndrome, type 1 diabetes mellitus and osteoporosis.
abstract: Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, skeletal abnormalities and hematological dysfunction. The genetic analysis of the SBDS gene and the long-term follow-up of a 37-year-old man with SDS, osteoporosis and type 1 diabetes are reported. Analysis of the SBDS gene revealed a compound heterozygous genotype with 7 mutations. This genotype is the result of the inheritance of abnormal alleles from both healthy parents. We identified putatively non-functional gene conversions from the SBDS pseudogene into the otherwise normal SBDS gene in each of the parentally inherited alleles. The association of SDS and type 1 diabetes mellitus seems to be coincidental and not associated to distinct mutations of the SBDS gene. Osteoporosis in patients with SDS may be the result of a primary defect of the bone metabolism and not of a nutritional problem, although our patient had chronic hypophosphatemia. The long-term follow-up of this patient provides interesting insights into the course of SDS, showing the complexity of genotype-phenotype correlations and the possible influence of other modifying genes and/or environmental factors that might determine the phenotypic presentation of SDS in an individual patient.
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitatsklinikum Leipzig, Leipzig, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Rosendahl
authors.forename: Niels
authors.initials: N
authors.lastname: Teich
authors.forename: Joachim
authors.initials: J
authors.lastname: Mossner
authors.forename: Jeanett
authors.initials: J
authors.lastname: Edelmann
authors.forename: Christian A
authors.initials: CA
authors.lastname: Koch
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology; D010188:Exocrine Pancreatic Insufficiency / Q000235:genetics / Q000473:pathology; D005192:Family Health; D005260:Female; D005785:Gene Conversion; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010024:Osteoporosis / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics*; D013577:Syndrome
chemical_list: D011506:Proteins; C470521:SBDS protein, human