The Italian National External Quality Assessment Program in Cytogenetics: 4 years of activity (2013-2016) following the introduction of poor performance criteria.

BACKGROUND: Italian External Quality Assessment (IEQA) Program in Cytogenetics, established in 2001 by the Istituto Superiore di Sanità (ISS), covers both Constitutional and Oncohaematological diagnosis. In 2013, performance criteria were defined and adopted. In this paper, we present the data from the first 4 years of activity (2013-2016) following the introduction of performance criteria. METHODS: The enrollment is voluntary, fee-based and open to both public and private Italian laboratories. The scheme is annual and retrospective; a national panel of experts assess technical, analytical and interpretative performance. RESULTS: Overall, 95 distinct Italian laboratories participated in different Cytogenetics IEQA schemes over the 2013-2016 years and most of the laboratories took part in Constitutional diagnosis. General hospitals and local health centers represented 40% of the total participants and the percentage of laboratories from Northern Regions was more than 45% of total participants throughout the 4-year period. As regards the performance evaluation, on average, 11, 9 and 23% of participants were marked as poor performers in Prenatal, Postnatal and Oncohaematological schemes, respectively. With regard to critical errors, ISCN nomenclature in Prenatal and Postnatal schemes, and interpretation in Oncohaematological diagnosis, were identified as main issues. On the other hand, karyotype errors and inadequate analysis decreased strongly, over the 4 years, in Constitutional and Oncohaematological diagnosis, respectively. CONCLUSIONS: Our data show that the introduction of poor performance encourages laboratories to address critical issues, and the IEQA participation helps to improve quality in cytogenetic testing.

De novo balanced chromosome rearrangements in prenatal diagnosis.

OBJECTIVE: We surveyed the datasheets of 29 laboratories concerning prenatal diagnosis of de novo apparently balanced chromosome rearrangements to assess the involvement of specific chromosomes, the breakpoints distribution and the impact on the pregnancy outcome. METHOD: By means of a questionnaire, data on 269.371 analyses performed from 1983 to 2006 on amniotic fluid, chorionic villus and fetal blood samples were collected. RESULTS: A total of 246 balanced anomalies were detected at frequencies of 72% for reciprocal translocations, 18% for Robertsonian translocations, 7% for inversions and 3% for complex chromosome rearrangements. The total frequencies of balanced rearrangements were 0.09%, 0.08% and 0.05% on amniotic fluid, chorionic villus and fetal blood samples. CONCLUSION: A preferential involvement of chromosomes 22, 7, 21, 3, 9 and 11 and a less involvement of chromosomes X, 19, 12, 6 and 1 was observed. A nonrandom distribution of the breakpoints across chromosomes was noticed. Association in the location of recurrent breakpoints and fragile sites was observed for chromosomes 11, 7, 10 and 22, while it was not recorded for chromosome 3. The rate of pregnancy termination was about 20%, with frequencies decreasing from complex chromosomal rearrangements (33%), reciprocal translocations (24%) to inversions (11%) and Robertsonian translocations (3%).

Cytogenetic and molecular evaluation of 241 small supernumerary marker chromosomes: cooperative study of 19 Italian laboratories.

PURPOSE: We evaluated the experiences of 19 Italian laboratories concerning 241 small supernumerary marker chromosomes (sSMCs) with the aim of answering questions arising from their origin from any chromosome, their variable size and genetic content, and their impact on the carrier's phenotype. METHODS: Conventional protocols were used to set up the cultures and chromosome preparations. Both commercial and homemade probes were used for the fluorescent in situ hybridization analyses. RESULTS: A total of 113 of the 241 sSMCs were detected antenatally, and 128 were detected postnatally. There were 52 inherited and 172 de novo cases. Abnormal phenotype was present in 137 cases (57%), 38 of which were antenatally diagnosed. A mosaic condition was observed in 87 cases (36%). In terms of morphology, monocentric and dicentric bisatellited marker chromosomes were the most common, followed by monocentric rings and short-arm isochromosomes. The chromosomes generating the sSMCs were acrocentric in 132 cases (69%) and non-acrocentric chromosomes in 60 cases (31%); a neocentromere was hypothesized in three cases involving chromosomes 6, 8, and 15. CONCLUSION: The presented and published data still do not allow any definite conclusions to be drawn concerning karyotype-phenotype correlations. Only concerted efforts to characterize molecularly the sSMCs associated or not with a clinical phenotype can yield results suitable for addressing karyotype-phenotype correlations in support of genetic counseling.