title: Genetic dosage compensation in a family with velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome.
abstract: Cytogenetic studies of a male child carrying the 22q11.2 deletion common in patients with velo-cardio-facial/DiGeorge syndrome showed an unexpected rearrangement of the 22q11.2 region in his normal appearing mother. The mother carried a 3 Mb deletion on one copy and a reciprocal, similar sized duplication on the other copy of chromosome 22q11.2 as shown by fluorescence in situ hybridization and array comparative genome hybridization analyses. The most parsimonious mechanism for the rearrangement is a mitotic non-allelic homologous recombination event in a cell in the early embryo soon after fertilization. The normal phenotype of the mother can be explained by the theory of genetic dosage compensation. This is the second documented case of such an event for this or any genomic disorder. This finding helps to reinforce this phenomenon in a human model, and has significant implications for recurrence risks for the dose-compensated mother.
authors.affiliation: Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.
authors.forename: Avishai A
authors.initials: AA
authors.lastname: Alkalay
authors.forename: Tingwei
authors.initials: T
authors.lastname: Guo
authors.forename: Cristina
authors.initials: C
authors.lastname: Montagna
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Digilio
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Bruno
authors.initials: B
authors.lastname: Marino
authors.forename: Bernice
authors.initials: B
authors.lastname: Morrow
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005190:Family; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy