Couple screening for recessively inherited disorders.

Couple screening aims to identify couples with an increased risk of having a child affected with an autosomal recessive or X-linked disorder, in order to facilitate informed reproductive decision making. Both expectant parents should be screened as a single entity, instead of individual testing. Carrier testing was typically performed for a few relatively common recessive disorders associated with significant morbidity, reduced life expectancy and often because of a considerably higher carrier frequency in a specific population for certain diseases. However, new genetic testing technologies enable the expansion of screening to multiple conditions, genes and sequence variants. There are multiple reproductive options for screening couples at risk, particularly when genetic traits are detected in the preconception period.

PALB2 germline mutations in a multi-gene panel testing cohort of 1905 breast-ovarian cancer patients in Argentina.

PURPOSE: PALB2 variants have been scarcely described in Argentinian and Latin-American reports. In this study, we describe molecular and clinical characteristics of PALB2 mutations found in multi-gene panels (MP) from breast-ovarian cancer (BOC) families in different institutions from Argentina. METHODS: We retrospectively identified PALB2 pathogenic (PV) and likely pathogenic (LPV) variants from a cohort of 1905 MP results, provided by one local lab (Heritas) and SITHER (Hereditary Tumor Information System) public database. All patients met hereditary BOC clinical criteria for testing, according to current guidelines. RESULTS: The frequency of PALB2 mutations is 2.78% (53/1905). Forty-eight (90.5%) are PV and five (9.5%) are LPV. Most of the 18 different mutations (89%) are nonsense and frameshift types and 2 variants are novel. One high-rate recurrent PV (Y551*) is present in 43% (23/53) of the unrelated index cases. From the 53 affected carriers, 94% have BC diagnosis with 14% of bilateral cases. BC phenotype is mainly invasive ductal (78%) with 62% of hormone-receptor positive and 22% of triple negative tumors. Self-reported ethnic background of the cohort is West European (66%) and native Latin-American (20%) which is representative of Buenos Aires and other big urban areas of the country. CONCLUSION: This is the first report describing molecular and clinical characteristics of PALB2 carriers in Argentina. Frequency of PALB2 PV in Argentinian HBOC families is higher than in other reported populations. Y551* is a recurrent mutation that seems to be responsible for almost 50% of PALB2 cases.

Genetic syndromes associated with isolated fetal growth restriction.

Early onset fetal growth restriction (FGR) may be due to impaired placentation, environmental or toxic exposure, congenital infections or genetic abnormalities. Remarkable research, mainly based on retrospective series, has been published on the diverse genetic causes. Those have become more and more relevant with the improvement in the accuracy of the analysis techniques and the rising of breakthrough genomewide methods such as the whole genome sequencing. However, no publication has presented an integrated view of management of those fetuses with an early and severe affection. In this review, we explored to which extent genetic syndromes can cause FGR fetuses without structural defects. The most common chromosomal abnormalities (Triploidies and Trisomy 18), submicroscopic chromosomal anomalies (22q11.2 microduplication syndrome) and single gene disorders (often associated with mild ultrasound findings) related to early and severe FGR had been analysed. Finally, we addressed the impact of epigenetic marks on fetal growth, a matter of growing importance. At the end of this review, we should be able to provide an adequate counseling to parents in terms of diagnosis, prognosis and management of those pregnancies.

Fetal cardiac abnormalities: Genetic etiologies to be considered.

Congenital heart diseases are a common prenatal finding. The prenatal identification of an associated genetic syndrome or a major extracardiac anomaly helps to understand the etiopathogenic diagnosis. Besides, it also assesses the prognosis, management, and familial recurrence risk while strongly influences parental decision to choose termination of pregnancy or postnatal care. This review article describes the most common genetic diagnoses associated with a prenatal finding of a congenital heart disease and a suggested diagnostic process.