An interstitial duplication of chromosome 13q31.3q32.1 further delineates the critical region for postaxial polydactyly type A2.

Postaxial polydactyly type A2 (PAP-A2; OMIM 602085) is a common feature seen in patients with a partial duplication of the long arm of chromosome 13. Dose dependency has been shown for digital malformations in this region, deletions resulting in oligodactyly and duplications in polydactyly. We aimed to narrow down the critical region for PAP-A2 in order to identify candidate genes.

Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype.

Purpose: To investigate the prognostic value of various cytogenetic components of a complex karyotype in acute myeloid leukemia (AML).

Patients And Methods: Cytogenetics and overall survival (OS) were analyzed in 1,975 AML patients age 15 to 60 years.

Results: Besides AML with normal cytogenetics (CN) and core binding factor (CBF) abnormalities, we distinguished 733 patients with cytogenetic abnormalities.

FISH and array-CGH analysis of a complex chromosome 3 aberration suggests that loss of CNTN4 and CRBN contributes to mental retardation in 3pter deletions.

Imbalances of 3p telomeric sequences cause 3p- and trisomy 3p syndrome, respectively, showing distinct, but also shared clinical features. No causative genes have been identified in trisomy 3p patients, but for the 3p- syndrome, there is growing evidence that monosomy for one or more of four genes at 3pter, CHL1, CNTN4, CRBN, and MEGAP/srGAP3, may play a causative role. We describe here an analysis of a complex chromosome 3p aberration in a severely mentally retarded patient that revealed two adjacent segments with different copy number gains and a distal deletion.

Application of a comprehensive subtelomere array in clinical diagnosis of mental retardation.

In 2-8% of patients with mental retardation, small copy number changes in the subtelomeric region are thought to be the underlying cause. As detection of these genomic rearrangements is labour intensive using FISH, we constructed and validated a high-density BAC/PAC array covering the first 5 Mb of all subtelomeric regions and applied it in our routine screening of patients with idiopathic mental retardation for submicroscopic telomeric rearrangements. The present study shows the efficiency of this comprehensive subtelomere array in detecting terminal deletions and duplications but also small interstitial subtelomeric rearrangements, starting from small amounts of DNA.

Selective chromosome analysis in couples with two or more miscarriages: case-control study.

Objective: To identify additional factors, such as maternal age or factors related to previous reproductive outcome or family history, and the corresponding probability of carrying a chromosome abnormality in couples with two or more miscarriages.

Design: Nested case-control study.

Setting: Six centres for clinical genetics in the Netherlands.