title: Apparent transmission distortion of a pericentric chromosome one inversion in a large multi-generation pedigree.
abstract: Pericentric chromosome inversions are often associated with infertility, recurrent pregnancy loss, and an increased risk for offspring with congenital anomalies. We report on a chromosome 1 inversion between 1p36.21 and 1q42.13, one of the largest described familial pericentric inversions of chromosome 1. The inversion was ascertained following the birth of a female with multiple congenital anomalies due to a recombinant chromosome 1. The inversion was subsequently detected or inferred in 16 healthy individuals over five generations. Interestingly, with a ratio of 16 carriers to 6 noncarriers, there appears to be transmission distortion of the inverted chromosome 1 within the family. Although there is no reported difficulty conceiving in the family, the risk of miscarriage is higher than predicted at 34% (13/38). The recurrence risk of a recombinant chromosome also appears to be lower than expected based on the mode of ascertainment. This case contributes to the spectrum of clinical features of chromosome 1 recombinants and raises the question of whether or not there is a selective advantage of the inverted chromosome at meiosis, conception, or post-zygotically that has contributed to transmission distortion of the inverted chromosome.
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Honeywell
authors.forename: Bob
authors.initials: B
authors.lastname: Argiropoulos
authors.forename: Stuart
authors.initials: S
authors.lastname: Douglas
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Blumenthal
authors.forename: Judith
authors.initials: J
authors.lastname: Allanson
authors.forename: Jean
authors.initials: J
authors.lastname: McGowan-Jordan
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: McCready
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D001344:Autopsy; D002871:Chromosome Banding; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D010375:Pedigree