Autosomal dominant transmission of familial laterality defects.
Heterotaxy results from failure to establish normal left-right asymmetry during embryonic development. Most familial cases are thought to be autosomal recessive. We have identified a family in which 4 individuals from 3 generations manifest laterality defects. Twenty-five family members have been examined. Two have complete reversal of normal laterality (situs inversus) while 2 others have asplenia, midline liver, and complex cardiac malformations (situs ambiguus). Two additional obligate gene carriers are anatomically normal (situs solitus). Male-to-male transmission confirms autosomal inheritance. Identification of this family establishes an autosomal dominant form of laterality defect, suggesting that a portion of sporadic cases may be new-mutation dominant or unrecognized familial cases. The finding of all forms of laterality (solitus, ambiguus, and inversus) among obligate disease gene carriers within a single family may be relevant to genetic evaluation and counseling in apparently isolated patients with laterality disturbance.
Casey
B
B
Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston 77030-3498, USA.
Cuneo
B F
BF
Vitali
C
C
van Hecke
H
H
Barrish
J
J
Hicks
J
J
Ballabio
A
A
Hoo
J J
JJ
D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D010375:Pedigree; D012857:Situs Inversus / Q000235:genetics*