Evolution of a prenatal genetic clinic-A 10-year cohort study.

OBJECTIVE: To (a) evaluate the proportion of women where a unifying genetic diagnosis was obtained following assessment of an observed pattern of fetal anomalies and (b) assess trends in genetic testing in a joint fetal-medicine genetic clinic. METHOD: Retrospective cohort study of all women attending the clinic. Outcomes included (a) indication for referral, (b) genetic test performed and (c) diagnoses obtained. RESULTS: From 2008 to 2019, 256 patients were referred and reviewed, of which 23% (n = 59) were consanguineous. The main indication for referral was the observed pattern of fetal anomalies. Over 10 years, the number of patients reviewed increased from 11 to 35 per annum. A unifying genetic diagnosis was obtained in 43.2% (n = 79/183), the majority of which were diagnosed prenatally (50.6% [n = 40/79]). The main investigation(s) that was the ultimate diagnostic test was targeted gene panel sequencing 34.2% (n = 27/79), with this and exome sequencing becoming the dominant genetic test by 2019. Pregnancies reviewed due to an abnormal karyotype or microarray decreased as an indication for referral during the study period (21.6% [n = 16/74] 2008-2012 vs 16.5% [n = 30/182] in 2012-2019). CONCLUSION: A prenatal genetic clinic with a structured multi-disciplinary team approach may be successful in obtaining a unifying prenatal genetic diagnosis.

Pandora's pregnancy: NIPT, CMA, and genome sequencing-A new era for prenatal genetic testing.

OBJECTIVES: We delineate in this article a shift from the "traditional" technologies of karyotyping in PND to the current phase of advanced genetic technologies including noninvasive prenatal testing (NIPT), chromosomal microarray analysis (CMA), and whole-exome sequencing (WES) with their higher detection rate and related abundance of uncertain data. METHODS: Conceptual analysis based on seminal works that shaped the socioethical discourse surrounding the experiences of parents as well as professionals with prenatal diagnosis in the last 30 years. RESULTS: We consider the implications of this new era of PND for patients and health professionals by drawing on previous studies documenting how probability and uncertainty affect informed consent/choice, health risks communication, customer satisfaction and decision making, and parent-child bonding. CONCLUSIONS: We argue that these changes move us beyond the idioms and realities of the tentative pregnancy and moral pioneering, to uncertainty, probability-based counseling, and moral/translational gambling. We conclude by discussing what is needed to maintain hope in the era of Pandora's pregnancy.

Where are we going with gene screening for male infertility?

Male infertility is a heterogenous disease process requiring the proper functioning and interaction of thousands of genes. Given the number of genes involved, it is thought that genetic causes contribute to most cases of infertility. Identifying these causes, however, is challenging. Infertility is associated with negative health outcomes, such as cancer, highlighting the need to further understand the genetic underpinnings of this condition. This paper describes the genetic and genomic tests currently available to identify the etiology of male infertility and then will discuss emerging technologies that may facilitate diagnosis and treatment of in the future.

An Overview on Prenatal Screening for Chromosomal Aberrations.

This article is a review of current and emerging methods used for prenatal detection of chromosomal aneuploidies. Chromosomal anomalies in the developing fetus can occur in any pregnancy and lead to death prior to or shortly after birth or to costly lifelong disabilities. Early detection of fetal chromosomal aneuploidies, an atypical number of certain chromosomes, can help parents evaluate their pregnancy options. Current diagnostic methods include maternal serum sampling or nuchal translucency testing, which are minimally invasive diagnostics, but lack sensitivity and specificity. The gold standard, karyotyping, requires amniocentesis or chorionic villus sampling, which are highly invasive and can cause abortions. In addition, many of these methods have long turnaround times, which can cause anxiety in mothers. Next-generation sequencing of fetal DNA in maternal blood enables minimally invasive, sensitive, and reasonably rapid analysis of fetal chromosomal anomalies and can be of clinical utility to parents. This review covers traditional methods and next-generation sequencing techniques for diagnosing aneuploidies in terms of clinical utility, technological characteristics, and market potential.

[Antenatal diagnosis: the revolution of new technologies]. / Gynécologie-obstétrique. Diagnostic prenatal: la révolution des nouvelles technologies.

Since ten years, the number of amniocenteses or chorionic villous sampling for maternal anxiety has decreased thanks to the first trimester screening of trisomy 21 by ultrasound and maternal serum analysis. Two new tools have recently revolutionized antenatal screening and diagnosis: Analysing fetal DNA in maternal blood for chromosomes 21, 18 and 13 in order to avoid invasive fetal sampling and genomic comparative hybridization in order to diagnose deletions or duplications not detected by conventional caryotyping. These new technologies are dedicated to high-risk pregnancies, and have limitations. They do not replace ultrasound or first trimester screening. Information and ethics are central in antenatal screening and diagnosis.

Diagnóstico prenatal y array-CGH II: gestaciones de bajo riesgo / Array-CGH in prenatal diagnosis II: low-risk pregnancies

Recientemente, la tecnología conocida como array-CGH se ha establecido como una herramienta diagnóstica de primer orden para el estudio de pacientes con anomalías congénitas, retraso mental no filiado y otras enfermedades neurológicas. Sin embargo, su utilidad como técnica de primer uso en el campo prenatal está actualmente en fase de evaluación, especialmente en embarazos de bajo riesgo. En una población de 530 gestantes con embarazos de bajo riesgo se realizó, simultáneamente, cariotipo convencional y un estudio de array-CGH para el diagnóstico prenatal. Mientras que el cariotipo detectó 3 casos (0,5%) con alteraciones citogéneticas no equilibradas (una de ellas no definida), el array-CGH detectó 8 casos con este tipo de alteraciones (1,5%), identificando el cambio indefinido detectado por cariotipo. Este estudio demuestra positivamente que el array-CGH puede ser una herramienta útil en el diagnóstico prenatal en embarazos de bajo riesgo(AU)

The array-CGH technique has recently been established as a first-tier diagnostic test for studying patients with congenital anomalies, idiopathic mental retardation and other neurological disorders. However, its use in prenatal diagnosis is still being evaluated, especially in low-risk pregnancies. A study was conducted on a population of 530 low-risk pregnancy women using both conventional karyotype and array-CGH for prenatal diagnosis. Whereas conventional karyotype detected 3 foetuses (0.5%) with unbalanced cytogenetic aberrations (one of them was undefined), array-CGH detected 8 foetuses with copy number aberrations (1.5%), and positively identified the undefined cytogenetic aberration detected using karyotype. In conclusion, this study proposes array-CGH as a useful tool in prenatal diagnosis for low-risk pregnancies(AU)