TY - JOUR
T1 - Linkage of otopalatodigital syndrome type 2 (OPD2) to distal Xq28
T2 - Evidence for allelism with OPD1
AU - Robertson, Stephen P.
AU - Walsh, Sinead
AU - Oldridge, Michael
AU - Gunn, Tania
AU - Becroft, David
AU - Wilkie, Andrew O.M.
PY - 2001
Y1 - 2001
N2 - Otopalatodigital syndrome type 1 (OPD1) is an X-linked semidominant condition characterized by malformations of the skeleton, auditory apparatus, and palate. Previous studies have established linkage to a 16-cM region of Xq27-q28. A proposed allelic variant of OPD1, termed "OPD2," is associated with a more severe, frequently lethal phenotype with visceral and brain anomalies in addition to skeletal, auditory, and palatal defects. We report linkage of the OPD2 phenotype to a 2-cM region of distal Xq28 in a Maori kindred, with a maximum multipoint LOD score of 3.31 between the markers DXS1073 and DXS1108. This provides support for allelism between OPD1 and OPD2 and reduces the size of the disease interval to 1.8-2.1 Mb. We also demonstrate that female carriers of this disorder exhibit skewed inactivation that segregates with the high-risk haplotype and may be inversely related to the severity with which they manifest features of the disorder.
AB - Otopalatodigital syndrome type 1 (OPD1) is an X-linked semidominant condition characterized by malformations of the skeleton, auditory apparatus, and palate. Previous studies have established linkage to a 16-cM region of Xq27-q28. A proposed allelic variant of OPD1, termed "OPD2," is associated with a more severe, frequently lethal phenotype with visceral and brain anomalies in addition to skeletal, auditory, and palatal defects. We report linkage of the OPD2 phenotype to a 2-cM region of distal Xq28 in a Maori kindred, with a maximum multipoint LOD score of 3.31 between the markers DXS1073 and DXS1108. This provides support for allelism between OPD1 and OPD2 and reduces the size of the disease interval to 1.8-2.1 Mb. We also demonstrate that female carriers of this disorder exhibit skewed inactivation that segregates with the high-risk haplotype and may be inversely related to the severity with which they manifest features of the disorder.
UR - https://www.scopus.com/pages/publications/0034964530
U2 - 10.1086/321280
DO - 10.1086/321280
M3 - Article
C2 - 11398100
AN - SCOPUS:0034964530
SN - 0002-9297
VL - 69
SP - 223
EP - 227
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -