Does non-invasive prenatal testing affect the livebirth prevalence of Down syndrome in the Netherlands? A population-based register study.

Objective: To evaluate if non-invasive prenatal testing (NIPT) affects livebirth (LB) prevalence of Down syndrome (DS) in the Netherlands.

Method: Data from clinical genetics laboratories and the Working Party on Prenatal Diagnosis and Therapy (2014-2018) and previous published data (1991-2013) were used to assess trends for DS LB prevalence and reduction percentage (the net decrease in DS LBs resulting from selective termination of pregnancies). Statistics Netherlands provided general population data.

SNP array-based copy number and genotype analyses for preimplantation genetic diagnosis of human unbalanced translocations.

Preimplantation genetic diagnosis (PGD) for chromosomal rearrangements (CR) is mainly based on fluorescence in situ hybridisation (FISH). Application of this technique is limited by the number of available fluorochromes, the extensive preclinical work-up and technical and interpretative artefacts. We aimed to develop a universal, off-the-shelf protocol for PGD by combining single-nucleotide polymorphism (SNP) array-derived copy number (CN) determination and genotyping for detection of unbalanced translocations in cleavage-stage embryos.

MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions.

A partial deletion of chromosome band 2p25.3 (2pter) is a rarely described cytogenetic aberration in patients with intellectual disability (ID). Using microarrays we identified deletions of 2p25.

Formation of novel CENP-A domains on tandem repetitive DNA and across chromosome breakpoints on human chromosome 8q21 neocentromeres.

Endogenous human centromeres form on megabase-sized arrays of tandemly repeated alpha satellite DNA. Human neocentromeres form epigenetically at ectopic sites devoid of alpha satellite DNA and permit analysis of centromeric DNA and chromatin organization. In this study, we present molecular cytogenetic and CENP-A chromatin immunoprecipitation (ChIP) on CHIP analyses of two neocentromeres that have formed in chromosome band 8q21 each with a unique DNA and CENP-A chromatin configuration.

A translocation in acute lymphoblastic leukemia that cytogenetically mimics the recurrent MLL-AFF1 translocation and fuses SEPT11 to MLL.

A 55-year-old man sought care for aggressive acute lymphoblastic leukemia (ALL), which developed 8 years after he had received chemotherapeutic treatment for nephrotic syndrome. The sole cytogenetic abnormality observed in bone marrow-derived metaphases was a t(4;11)(q21;q23), which is a frequently occurring translocation in ALL. However, subsequent reverse transcriptase-polymerase chain reaction for the expected mixed lineage leukemia [trithorax homolog, Drosophila] (MLL)-AFF1 fusion transcript was negative.

The unfolding clinical spectrum of holoprosencephaly due to mutations in SHH, ZIC2, SIX3 and TGIF genes.

Holoprosencephaly is a severe malformation of the brain characterized by abnormal formation and separation of the developing central nervous system. The prevalence is 1:250 during early embryogenesis, the live-born prevalence is 1:16 000. The etiology of HPE is extremely heterogeneous and can be teratogenic or genetic.

Different distribution of the genetic subtypes of the Prader-Willi syndrome in the elderly.

The Prader-Willi syndrome (PWS) is a genetic disorder caused by the absent expression of the paternal copy of maternally imprinted genes in chromosome region 15q11-13. The frequencies of different subtypes in PWS are usually given in literature as 70% deletion, 25-30% maternal uniparental disomy (mUPD) and 3-5% others (imprinting centre (IC) defects and translocations). Little is known about factors that influence the frequency of genetic subtypes in PWS.

Identical cryptic partial monosomy 20pter and trisomy 20qter in three adult siblings due to a large maternal pericentric inversion: detection by MLPA and breakpoint mapping by SNP array analysis.

Genotypic and phenotypic data are presented on three adult siblings with mild to moderate mental retardation and mild dysmorphic features. All three siblings showed a chromosome 20 gain at the q-telomere and loss at the p-telomere in routine subtelomeric MLPA screening. Analysis of GTG-banded chromosomes did not detect any abnormalities, but subtelomeric fluorescent in situ hybridization (FISH) confirmed cryptic partial monosomy of chromosome region 20p13 --> 20pter and cryptic partial trisomy of chromosome region 20q13.

Kabuki syndrome is not caused by an 8p duplication: a cytogenetic study in 20 patients.

Kabuki syndrome is characterized by a typical facial gestalt in combination with hypotonia and joint laxity, developmental delay, persistent fetal fingertip pads, and structural abnormalities mainly of the palate and the heart. Cytogenetic conditions may present with features of the syndrome. Recently, Milunsky and Huang [2003], reported an 8p duplication at chromosome 8p22-8p23.

Familial cryptic translocation with deletion 4q33-->4qter and duplication 7q34-->7qter in brothers with mental retardation, macrocephaly and iris coloboma.

The association of moderate mental retardation, behavioural problems, macrocephaly, dysmorphic features with iris coloboma, and supernumerary nipples was observed in two brothers with a terminal deletion 4q33-->4qter and a terminal duplication 7q34-->7qter. The aberration was detected by subtelomere FISH screening and (probably) resulted from a cryptic familial translocation (4;7)(q33;q34).