Shwachman-Diamond syndrome with exocrine pancreatic dysfunction and bone marrow failure maps to the centromeric region of chromosome 7.
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 approximately 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.
Program in Genetics and Genomic Biology, Research Institute, and Departments of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada.
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Goobie
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M
Popovic
J
J
Morrison
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L
Ellis
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H
Ginzberg
G R
GR
Boocock
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N
Ehtesham
C
C
Bétard
C G
CG
Brewer
N M
NM
Roslin
T J
TJ
Hudson
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Morgan
T M
TM
Fujiwara
P R
PR
Durie
J M
JM
Rommens
D000483:Alleles; D001855:Bone Marrow Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002503:Centromere / Q000235:genetics*; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D010188:Exocrine Pancreatic Insufficiency / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive / Q000235:genetics; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D009139:Musculoskeletal Abnormalities / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics; D022423:Myeloid Cells / Q000473:pathology; D010375:Pedigree; D012984:Software; D013577:Syndrome