Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene, JAM3, expressed during cardiogenesis.
Hypoplastic left heart is a severe human congenital heart defect characterized by left ventricular hypoplasiawith aortic and mitral valve atresia. A genetic etiology is indicated by an association of the hypoplastic left heart phenotype with terminal 11q deletions that span approximately 20 Mb (distal to FRA11B in 11q23). Here we define the breakpoints in four patients with heart defects in association with distal 11q monosomy and refine the critical region to an approximately 9-Mb region distal to D11S1351. Within this critical region we have identified JAM3, a member of the junction adhesion molecule family, as a strong candidate gene for the cardiac phenotype on the basis that it is expressed during human cardiogenesis in the structures principally affected in hypoplastic left heart.
Phillips
Helen M
HM
Institute of Human Genetics, University of Newcastle Upon Tyne, NE1 382, UK.
Renforth
Glenn L
GL
Spalluto
Cosma
C
Hearn
Tom
T
Curtis
Andrew R J
AR
Craven
Lyndsey
L
Havarani
Beatrice
B
Clement-Jones
Mark
M
English
Carol
C
Stumper
Oliver
O
Salmon
Tony
T
Hutchinson
Susie
S
Jackson
Mike S
MS
Wilson
David I
DI
D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D006321:Heart / Q000196:embryology* / Q000502:physiology; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000235:genetics*; D007136:Immunoglobulins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009928:Organ Specificity; D017354:Point Mutation; D017384:Sequence Deletion
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C448000:JAM3 protein, human; D008565:Membrane Proteins