title: Molecular analysis of velo-cardio-facial syndrome patients with psychiatric disorders.
abstract: Velo-cardio-facial syndrome (VCFS) is characterized by conotruncal cardiac defects, cleft palate, learning disabilities, and characteristic facial appearance and is associated with hemizygous deletions within 22q11. A newly recognized clinical feature is the presence of psychiatric illness in children and adults with VCFS. To ascertain the relationship between psychiatric illness, VCFS, and chromosome 22 deletions, we evaluated 26 VCFS patients by clinical and molecular biological methods. The VCFS children and adolescents were found to share a set of psychiatric disorders, including bipolar spectrum disorders and attention-deficit disorder with hyperactivity. The adult patients, >18 years of age, were affected with bipolar spectrum disorders. Four of six adult patients had psychotic symptoms manifested as paranoid and grandiose delusions. Loss-of-heterozygosity analysis of all 26 patients revealed that all but 3 had a large 3-Mb common deletion. One patient had a nested distal deletion and two did not have a detectable deletion. Somatic cell hybrids were developed from the two patients who did not have a detectable deletion within 22q11 and were analyzed with a large number of sequence tagged sites. A deletion was not detected among the two patients at a resolution of 21 kb. There was no correlation between the phenotype and the presence of the deletion within 22q11. The remarkably high prevalence of bipolar spectrum disorders, in association with the congenital anomalies of VCFS and its occurrence among nondeleted VCFS patients, suggest a common genetic etiology.
authors.affiliation: Department of Molecular Genetics, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA.
authors.forename: C
authors.initials: C
authors.lastname: Carlson
authors.forename: D
authors.initials: D
authors.lastname: Papolos
authors.forename: R K
authors.initials: RK
authors.lastname: Pandita
authors.forename: G L
authors.initials: GL
authors.lastname: Faedda
authors.forename: S
authors.initials: S
authors.lastname: Veit
authors.forename: R
authors.initials: R
authors.lastname: Goldberg
authors.forename: R
authors.initials: R
authors.lastname: Shprintzen
authors.forename: R
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: B
authors.initials: B
authors.lastname: Morrow
mesh_terms: D000015:Abnormalities, Multiple / Q000209:etiology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22; D005145:Face / Q000002:abnormalities; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D001523:Mental Disorders / Q000209:etiology / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: D005819:Genetic Markers