RT Journal Article
SR Electronic
T1 Familial 4.3 Mb duplication of 21q22 sheds new light on the Down syndrome critical region
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 448
OP 451
DO 10.1136/jmg.2006.047373
VO 44
IS 7
A1 Anne Ronan
A1 Kerry Fagan
A1 Louise Christie
A1 Jeffrey Conroy
A1 Norma J Nowak
A1 Gillian Turner
YR 2007
UL http://jmg.bmj.com/content/44/7/448.abstract
AB 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.