title: 3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome.
abstract: We report the identification of six patients with 3q29 microdeletion syndrome. The clinical phenotype is variable despite an almost identical deletion size. The phenotype includes mild-to-moderate mental retardation, with only slightly dysmorphic facial features that are similar in most patients: a long and narrow face, short philtrum, and high nasal bridge. Autism, gait ataxia, chest-wall deformity, and long and tapering fingers were noted in at least two of six patients. Additional features--including microcephaly, cleft lip and palate, horseshoe kidney and hypospadias, ligamentous laxity, recurrent middle ear infections, and abnormal pigmentation--were observed, but each feature was only found once, in a single patient. The microdeletion is approximately 1.5 Mb in length, with molecular boundaries mapping within the same or adjacent bacterial artificial chromosome (BAC) clones at either end of the deletion in all patients. The deletion encompasses 22 genes, including PAK2 and DLG1, which are autosomal homologues of two known X-linked mental retardation genes, PAK3 and DLG3. The presence of two nearly identical low-copy repeat sequences in BAC clones on each side of the deletion breakpoint suggests that nonallelic homologous recombination is the likely mechanism of disease causation in this syndrome.
authors.affiliation: Department of Medical Genetics, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Lionel
authors.initials: L
authors.lastname: Willatt
authors.forename: James
authors.initials: J
authors.lastname: Cox
authors.forename: John
authors.initials: J
authors.lastname: Barber
authors.forename: Elisabet Dachs
authors.initials: ED
authors.lastname: Cabanas
authors.forename: Amanda
authors.initials: A
authors.lastname: Collins
authors.forename: Dian
authors.initials: D
authors.lastname: Donnai
authors.forename: David R
authors.initials: DR
authors.lastname: FitzPatrick
authors.forename: Eddy
authors.initials: E
authors.lastname: Maher
authors.forename: Howard
authors.initials: H
authors.lastname: Martin
authors.forename: Josep
authors.initials: J
authors.lastname: Parnau
authors.forename: Lesley
authors.initials: L
authors.lastname: Pindar
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ramsay
authors.forename: Charles
authors.initials: C
authors.lastname: Shaw-Smith
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: Michael
authors.initials: M
authors.lastname: Tettenborn
authors.forename: Dorothy
authors.initials: D
authors.lastname: Trump
authors.forename: Bert B A
authors.initials: BB
authors.lastname: de Vries
authors.forename: Kate
authors.initials: K
authors.lastname: Walker
authors.forename: F Lucy
authors.initials: FL
authors.lastname: Raymond
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D019465:Craniofacial Abnormalities / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D010641:Phenotype; D013577:Syndrome