Background. Several studies observed metabolic disorders in pregnancy as risk factors for birth defects, including orofacial clefts. Diabetes is associated with approx. 10% of the pregnancies, but in Romania, less than 5%. An obese and diabetic woman has 3 times more risk for an offspring with a craniofacial defect than healthy women suggesting that diabetes mellitus contributes to their pathogenesis with complex mechanisms. Case report. We present the case of a newborn 4 days old, male with neonatal hypoglycemia, cleft lip and proportionate (symmetric) macrosomia. His mother is a 35 years old Caucasian woman with no important personal risk factors and no known history of diabetes mellitus. The glucose tolerance test performed to the mother at about 10 weeks during pregnancy led to the diagnosis of gestational diabetes. Discussion. The gestational diabetes mellitus diagnosed since the 10 th week of pregnancy, the hyperglycemia status during pregnancy and the fetal overgrowth (macrosomia at birth) indicate the possible factors that lead to the Orofacial cleft (OFC). Conclusion. With the increased prevalence of obesity, diabetes, and the evidence of association of these syndromes with OFCs, it is recommended that mothers planning to become pregnant to follow healthy habits, maintain healthy weight, and be screened for possible diabetes prior to conception and early in pregnancy.

Two familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1,MSH2,MSH6,PMS2) and the genes APC and MUTYH, respectively. No information is available on the presence of high‐risk CRC mutations in the Romanian population. We performed whole‐genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical (IHC) staining for MLH1,MSH2,MSH6, and PMS2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH1, one in MSH6, one in PMS2, and three in APC. Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants (MLH1:p.Lys84ThrfsTer4, MLH1:p.Ala586CysfsTer7, PMS2:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH1:c.1559‐1G>C).

Background/Aim: The aim of the study was to report the case of a 5-month-old boy with a complex prenatal and neonatal symptomatology diagnosed with a “de novo" pathogenic variant of PUF60 gene. Case Report: Our hospital, undertook the antenatal and postnatal care of a 27-year-old pregnant lady. This was her second baby with a previously healthy boy. During her routine first-trimester anomaly scan, increased nuchal translucency was noticed. Multiple anomalies were seen throughout her subsequent antenatal visits. This triggered a sequence of tests, examinations and differential diagnosis. The final diagnosis was made at 5 months postpartum following the result of the whole exome sequence, which described a variant of unknown clinical significance (VUS, class 3 variant) in the PUF60 gene. We are mindful that changing the classification of a variant of unknown significance is challenging and requires supporting and robust criteria. Considering clinical symptomatology produced by the pathogenic mutation in the PUF gene, the identified c.1640A>G variant may be categorized as likely pathogenic. Conclusion: Our case adds new insights on the pathology and the underlying process involved in the PUF60 variant spectrum disorders. It also highlights the limits of current prenatal tests.

No abstract

To find sequence variants affecting prostate cancer (PCA) susceptibility in an unscreened Romanian population we use a genome‐wide association study (GWAS). The study population included 990 unrelated pathologically confirmed PCA cases and 1034 male controls. DNA was genotyped using Illumina SNP arrays, and 24.295.558 variants were imputed using the 1000 Genomes data set. An association test was performed between the imputed markers and PCA. A systematic literature review for variants associated with PCA risk identified 115 unique variants that were tested in the Romanian sample set. Thirty of the previously reported SNPs replicated (P‐value < 0.05), with the strongest associations observed at: 8q24.21, 11q13.3, 6q25.3, 5p15.33, 22q13.2, 17q12 and 3q13.2. The replicated variants showing the most significant association in Romania are rs1016343 at 8q24.21 (P = 2.2 × 10−4), rs7929962 at 11q13.3 (P = 2.7 × 10−4) and rs9364554 at 6q25.2 (P = 4.7 × 10−4). None of the variants tested in the Romanian GWAS reached genome‐wide significance (P‐value <5 × 10−8) but 807 markers had P‐values <1 × 10−4. Here, we report the results of the first GWAS of PCA performed in a Romanian population. Our study provides evidence that a substantial fraction of previously validated PCA variants associate with risk in this unscreened Romanian population.