Shwachman-Diamond Syndrome with Exocrine Pancreatic Dysfunction and Bone Marrow Failure Maps to the Centromeric Region of Chromosome 7

• Published in: American journal of human genetics Vol. 68; no. 4; pp. 1048 - 1054
• Main Authors: Goobie, Sharan, Popovic, Maja, Morrison, Jodi, Ellis, Lynda, Ginzberg, Hedy, Boocock, Graeme R.B., Ehtesham, Nadia, Bétard, Christine, Brewer, Carl G., Roslin, Nicole M., Hudson, Thomas J., Morgan, Kenneth, Fujiwara, T. Mary, Durie, Peter R., Rommens, Johanna M.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.04.2001; University of Chicago Press; The American Society of Human Genetics
• Subjects: Alleles; Biological and medical sciences; Bone Marrow Diseases - blood; Bone Marrow Diseases - genetics; Bone Marrow Diseases - pathology; Centromere - genetics; Chromosome Mapping; Chromosomes, Human, Pair 7 - genetics; Exocrine Pancreatic Insufficiency - genetics; Exocrine Pancreatic Insufficiency - pathology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; Genes, Recessive - genetics; Genetic Heterogeneity; Genetic Linkage - genetics; Haplotypes - genetics; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lod Score; Male; Medical sciences; Models, Genetic; Musculoskeletal Abnormalities - genetics; Musculoskeletal Abnormalities - pathology; Mutation - genetics; Myeloid Cells - pathology; Other diseases. Semiology; Pedigree; Software; Syndrome; Human; Linkage; Leukopenia; Family study; Pathogenesis; Diseases of the osteoarticular system; Hemopathy; Exocrine pancreas insufficiency; Chromosome C7; Congenital disease; Genetic determinism; Growth retardation; Genetic disease; Shwachman Diamond syndrome; Concomitant disease; Phenotype; Gene; Autosomal character; Digestive diseases; Recessive character; Complex syndrome; Locus; Pancreatic disease; Neutropenia
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/319505

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency and hematologic and skeletal abnormalities. A genomewide scan of families with SDS was terminated at ∼50% completion, with the identification of chromosome 7 markers that showed linkage with the disease. Finer mapping revealed significant linkage across a broad interval that included the centromere. The maximum two-point LOD score was 8.7, with D7S473, at a recombination fraction of 0. The maximum multipoint LOD score was 10, in the interval between D7S499 and D7S482 (5.4 cM on the female map and 0 cM on the male map), a region delimited by recombinant events detected in affected children. Evidence from all 15 of the multiplex families analyzed provided support for the linkage, consistent with a single locus for SDS. However, the presence of several different mutations is suggested by the heterogeneity of disease-associated haplotypes in the candidate region.