TY - JOUR
T1 - Genetic and physical mapping of the McKusick-Kaufman syndrome
AU - Stone, Deborah L.
AU - Agarwala, Richa
AU - Schäffer, Alejandro A.
AU - Weber, James L.
AU - Vaske, David
AU - Oda, Takaya
AU - Chandrasekharappa, Settara C.
AU - Francomano, Clair A.
AU - Biesecker, Leslie G.
PY - 1998/3
Y1 - 1998/3
N2 - McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos,.This syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and variable expressivity. Homozygosity mapping and linkage analyses were conducted using two pedigrees derived from a larger pedigree published in 1978. The PedHunter software query system was used on the Amish Genealogy Database to correct the previous pedigree, derive a minimal pedigree connecting those affected sibships that are in the database and determine the most recent common ancestors of the affected persons. Whole genome short tandem repeat polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and D20S894, an area that includes the Alagille syndrome critical region. The peak two-point LOD score was 3.33, and the peak three-point LOD score was 5.21. The physical map of this region has been defined, and additional polymorphic markers have been isolated. The region includes several genes and expressed sequence tags (ESTs), including the jagged1 gene that recently has been shown to be haploinsufficient in the Alagille syndrome. Sequencing of jagged1 in two unrelated individuals affected with McKusick-Kaufman syndrome has not revealed any disease-causing mutations.
AB - McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos,.This syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and variable expressivity. Homozygosity mapping and linkage analyses were conducted using two pedigrees derived from a larger pedigree published in 1978. The PedHunter software query system was used on the Amish Genealogy Database to correct the previous pedigree, derive a minimal pedigree connecting those affected sibships that are in the database and determine the most recent common ancestors of the affected persons. Whole genome short tandem repeat polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and D20S894, an area that includes the Alagille syndrome critical region. The peak two-point LOD score was 3.33, and the peak three-point LOD score was 5.21. The physical map of this region has been defined, and additional polymorphic markers have been isolated. The region includes several genes and expressed sequence tags (ESTs), including the jagged1 gene that recently has been shown to be haploinsufficient in the Alagille syndrome. Sequencing of jagged1 in two unrelated individuals affected with McKusick-Kaufman syndrome has not revealed any disease-causing mutations.
UR - http://www.scopus.com/inward/record.url?scp=0031909968&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031909968&partnerID=8YFLogxK
U2 - 10.1093/hmg/7.3.475
DO - 10.1093/hmg/7.3.475
M3 - Article
C2 - 9467007
AN - SCOPUS:0031909968
SN - 0964-6906
VL - 7
SP - 475
EP - 481
JO - Human molecular genetics
JF - Human molecular genetics
IS - 3
ER -