Euchromatic 9q13-q21 duplication variants are tandem segmental amplifications of sequence reciprocal to 9q13-q21 deletions.

BACKGROUND: There are four known pericentromeric euchromatic variants of chromosome 9 in the literature that are increasingly being observed in diagnostic cytogenetic laboratories. These variants pose diagnostic and counselling dilemmas, especially in prenatal settings, as distinction of a pathogenic alteration from a euchromatic variant is difficult. The molecular characterisation of three of these four variants has been reported. In this study, the genomic structure of the fourth variant, an additional G-positive band at 9q13-q21, is characterised. METHODS: Two unrelated families with the 9q13-q21 duplication variant, and a third individual with a cytogenetically visible 9q13-q21 deletion, were studied using conventional and molecular cytogenetics techniques, as well as microarrays. The highly repetitive nature of the segmental duplications in the region also necessitated the use of both interphase and metaphase fluorescence in situ hybridisation (FISH). RESULTS: It was determined that the DNA that constitutes this variant was ∼ 15-20 megabases in size and tandemly repeated as 3-4 cassettes of intrachromosomal segmental duplication. The variant appeared constitutively similar in sequence content and organisation between the two unrelated individuals, and it was inherited without apparent change. Sequences found amplified in the two duplication carriers were absent in the carrier of the deletion variant. CONCLUSIONS: The sequences involved in both the 9q13-q21 duplication and deletion appear the same, implying reciprocity and suggesting non-allelic homologous recombination as the underlying mechanism. All four known euchromatic variants of chromosome 9 have now been shown to encompass segmental duplications. Importantly, a set of validated FISH probes was defined for the detection and characterisation of this 9q13-q21 amplification in the context of other chromosome 9 variants, allowing apparently benign variants to be distinguished from pathogenic changes.

Tetrasomy 9p mosaicism associated with a normal phenotype.

Isochromosome (tetrasomy) 9p is a rare chromosomal aberration characterized by phenotypic abnormalities ranging from mild developmental delay to multiple anomalies including intrauterine growth retardation, cerebral ventriculomegaly, dysmorphic facial features, cleft lip or palate, abnormal genitalia and renal anomalies. We present a patient with isochromosome (tetrasomy) 9p mosaicism who is a healthy normal adult male with oligospermia who has fathered two normal children. This chromosomal abnormality may be tissue specific, with a higher detection rate in cultured lymphocytes compared with fibroblasts. Therefore, there is an increased chance of missing the abnormality prenatally by amniocentesis or chorionic villus sampling. We are aware of only one other patient in the literature with a normal phenotype associated with mosaicism for this chromosomal abnormality.

Success rate for culture of fetal postmortem tissue is dependent on the method of pregnancy termination.

OBJECTIVE: To determine the effect of different methods of pregnancy termination on the culture success rate of postmortem fetal tissue. METHODS: In a randomized trial, umbilical cord specimens were collected in a standardized manner and culture success rates were compared according to the method of pregnancy termination. RESULTS: There was a significantly higher culture success rate in the vaginal (90.0%) and oral misoprostol (83.0%) groups compared to the intra-amniotic injection of prostaglandin group (52.8%). CONCLUSION: The results of our study and the very high success rate reported by others from specimens following dilatation and evacuation lead us to suggest that exposure to drugs used to induce abortion may be a more important factor in culture failure than either tissue type or time in transit.

A randomised controlled trial of biopsy forceps and cannula aspiration for transcervical chorionic villus sampling.

OBJECTIVE: This trial compared two instruments for transcervical chorionic villus sampling (CVS). DESIGN: Randomised controlled trial. SETTING: Regional university prenatal diagnosis and treatment centre. POPULATION: Two hundred women were randomised at 10(+0)-12(+6) weeks of gestation to transcervical CVS using cannula aspiration (CA) or biopsy forceps (BF). METHODS: Women undergoing indicated CVS signed informed consent. Randomisation after decision to perform transcervical CVS. PRIMARY OUTCOME: the rise in maternal serum alpha-fetoprotein (alpha-FP). SECONDARY OUTCOMES: (i) placental trauma (fetomaternal haemorrhage [FMH]); (ii) laboratory, procedure, and cytogenetic results and pregnancy outcomes; (iii) patient and operator satisfaction; and (iv) economic analyses. Analyses were performed by intention to treat. RESULTS: The -FP rise did not differ between groups; there was no other evidence of placental trauma. BF were better tolerated by women, provided culturable tissue, after fewer instrument passes, with greater ease and in less time. BF were associated with cost savings. CONCLUSIONS: Unlike -FP, other markers of FMH were unaltered, questioning the reliability of alpha-FP as an indicator of FMH. Compared with CA, transcervical BF caused comparable placental trauma, appeared to be similarly effective and safe and were preferred by operators and patients.