title: Higher frequency of uncommon 1.5-2 Mb deletions found in familial cases of 22q11.2 deletion syndrome.
abstract: Familial 22q11.2 deletions have been reported as a 6%-28% of the total affected cases of 22q11.2 microdeletion syndrome (del22q11.2). Different deletion genotypes have been described for this disorder, with a predominant 3 Mb deletion present in 90% of the cases, a less common 1.5-2 Mb deletion in 8%, and atypical smaller deletions in 2%. We have studied 15 cases of del22q11.2 from 6 families (two of them three-generation families) that were previously diagnosed through FISH. We have sized the deleted region by allele genotyping of 12-16 polymorphic markers in all cases, and we have found three families affected with the 1.5-2 Mb deletion, two affected with the 3 Mb deletion, and one in which the deletion size could not be determined. This predominance of the smaller 1.5-2 Mb deletions in our familial cases differs from the minor frequency observed in sporadic cases of del22q11.2. This finding suggests that small deletions are more linked to familial inheritance than large ones, possibly due to psychosocial or biological factors associated with differences in the phenotype. Deletion sizing on routine diagnosis may help characterizing the inheritability of 22q11.2 microdeletion syndrome.
authors.affiliation: Servicio de Genética Médica, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Fernández
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.forename: Isidora López
authors.initials: IL
authors.lastname: Pajares
authors.forename: Germán Rodríguez
authors.initials: GR
authors.lastname: Criado
authors.forename: Luis
authors.initials: L
authors.lastname: García-Guereta
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez
authors.forename: José
authors.initials: J
authors.lastname: Quero
authors.forename: Alicia
authors.initials: A
authors.lastname: Delicado
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D005192:Family Health; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D010159:Palate / Q000002:abnormalities; D013577:Syndrome; D013771:Tetralogy of Fallot / Q000473:pathology