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.
Goobie
S
S
Program in Genetics and Genomic Biology, Research Institute, and Departments of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada.
Popovic
M
M
Morrison
J
J
Ellis
L
L
Ginzberg
H
H
Boocock
G R
GR
Ehtesham
N
N
Bétard
C
C
Brewer
C G
CG
Roslin
N M
NM
Hudson
T J
TJ
Morgan
K
K
Fujiwara
T M
TM
Durie
P R
PR
Rommens
J M
JM
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