March 1, 1995Circulation
Genetic Heterogeneity of Heart-Hand Syndromes
Key result
Holt-Oram syndrome maps to chromosome 12q2, unlike phenotypically similar conditions like heart-hand syndrome type III.
- odds >10(25):1
Why the study?
The genetic basis of related heart-hand syndromes such as heart-hand syndrome type III and familial atrial septal defects with conduction disease is unknown compared to Holt-Oram syndrome.
Population
Five kindreds with Holt-Oram syndrome, one kindred with heart-hand syndrome type III, one kindred with familial atrial septal defect and conduction disease
Comparison
Holt-Oram syndrome versus heart-hand syndrome type III and familial atrial septal defect with conduction disease
Design
Clinical evaluations and genetic linkage analyses in observational study
Authors
Discussion
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Implication
Mapping to 12q does not alter care for heart-hand syndromes; leaves open whether this locus drives conduction disease in related disorders.
Key Points
- To determine whether the chromosome 12q2 locus linked to Holt-Oram syndrome is also responsible for related conditions including heart-hand syndrome type III and familial atrial septal defects.
- Performed clinical evaluations and genetic linkage analyses in five families with Holt-Oram syndrome.
- Evaluated one family with heart-hand syndrome type III and one family with familial atrial septal defect and cardiac conduction disease for linkage to chromosome 12q2.
- Holt-Oram syndrome mapped to chromosome 12q2 in all five kindreds, providing cumulative odds greater than 10^25:1 that the disease gene resides at this locus.
- Neither heart-hand syndrome type III nor familial atrial septal defect with atrioventricular block mapped to chromosome 12q2, establishing that these disorders are genetically distinct from Holt-Oram syndrome.
Study Design
Type
Observational
Structured PICO
P
Population
Seven kindreds with Holt-Oram syndrome, heart-hand syndrome type III, or familial atrial septal defect undergoing clinical evaluation and genetic linkage analysis.
E
Exposure
Clinical evaluations and genetic linkage analyses
O
Outcome
Genetic mapping to chromosome 12q2surrogate
Main Result
Effect estimate: odds >10(25):1
Heart-hand syndromes are genetically heterogeneous, with Holt-Oram syndrome mapping to chromosome 12q2, while phenotypically similar conditions arise from distinct genetic loci.
Cite This Study
Basson et al. (1995) conducted an observational in Heart-hand syndromes (Holt-Oram syndrome, heart-hand syndrome type III, familial atrial septal defect). Genetic linkage analysis was evaluated on Mapping to chromosome 12q2 (odds >10(25):1). Genetic linkage analysis demonstrated that Holt-Oram syndrome maps to chromosome 12q2 (odds >10(25):1), whereas phenotypically similar conditions like heart-hand syndrome type III do not.