title: Familial 4.3 Mb duplication of 21q22 sheds new light on the Down syndrome critical region.
abstract: A 4.3 Mb duplication of chromosome 21 bands q22.13-q22.2 was diagnosed by interphase fluorescent in-situ hybridisation (FISH) in a 31-week gestational age baby with cystic hygroma and hydrops; the duplication was later found in the mother and in her 8-year-old daughter by the same method and confirmed by array comparative genomic hybridisation (aCGH). All had the facial gestalt of Down syndrome (DS). This is the smallest accurately defined duplication of chromosome 21 reported with a DS phenotype. The duplication encompasses the gene DYRK1 but not DSCR1 or DSCAM, all of which have previously been implicated in the causation of DS. Previous karyotype analysis and telomere screening of the mother, and karyotype analysis and metaphase FISH of a chorionic villus sample, had all failed to reveal the duplication. The findings in this family add to the identification and delineation of a "critical region" for the DS phenotype on chromosome 21. Cryptic chromosomal abnormalities can be missed on a routine karyotype for investigation of abnormal prenatal ultrasound findings, lending support to the use of aCGH analysis in this setting.
authors.forename: Anne
authors.initials: A
authors.lastname: Ronan
authors.forename: Kerry
authors.initials: K
authors.lastname: Fagan
authors.forename: Louise
authors.initials: L
authors.lastname: Christie
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Conroy
authors.forename: Norma J
authors.initials: NJ
authors.lastname: Nowak
authors.forename: Gillian
authors.initials: G
authors.lastname: Turner
mesh_terms: D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D005333:Fetus; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000097603:Dyrk Kinases
chemical_list: D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases