Molecular investigation of familial Beckwith-Wiedemann syndrome: a model for paternal imprinting.
In familial Beckwith-Wiedemann syndrome (BWS), the mode of inheritance is uncertain and possible patterns include autosomal dominant, multifactorial and autosomal dominant sex-dependent inheritance. Genomic imprinting has recently been invoked to explain the unusual inheritance patterns in several disorders. We have previously reviewed 28 published kindreds of BWS and shown that paternal imprinting is probably responsible for familial BWS. In the present paper, highly informative RFLP markers in the 11p15.5 region have been shown to segregate with the disease gene as an autosomal dominant, but phenotypic manifestations in an offspring are dependent on the sex of the parent contributing the defective gene. In contrast to previous reports in which imprinting of the growth stimulator gene, IGF2, has been invoked as the mechanism explaining sporadic cases of BWS (especially in situations where uniparental disomy and trisomy of the 11p15.5 region has occurred), it is suggested that paternal imprinting of a growth suppressor gene, e.g., H19, may be one of the causes of familial BWS.
Ramesar
R
R
Department of Human Genetics, University of Cape Town Medical School, South Africa.
Babaya
M
M
Viljoen
D
D
D000483:Alleles; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D013019:South Africa