Broadening the phenotypic and molecular spectrum of FINCA syndrome: Biallelic NHLRC2 variants in 15 novel individuals.

FINCA syndrome [MIM: 618278] is an autosomal recessive multisystem disorder characterized by fibrosis, neurodegeneration and cerebral angiomatosis. To date, 13 patients from nine families with biallelic NHLRC2 variants have been published. In all of them, the recurrent missense variant p.(Asp148Tyr) was detected on at least one allele. Common manifestations included lung or muscle fibrosis, respiratory distress, developmental delay, neuromuscular symptoms and seizures often followed by early death due to rapid disease progression.Here, we present 15 individuals from 12 families with an overlapping phenotype associated with nine novel NHLRC2 variants identified by exome analysis. All patients described here presented with moderate to severe global developmental delay and variable disease progression. Seizures, truncal hypotonia and movement disorders were frequently observed. Notably, we also present the first eight cases in which the recurrent p.(Asp148Tyr) variant was not detected in either homozygous or compound heterozygous state.We cloned and expressed all novel and most previously published non-truncating variants in HEK293-cells. From the results of these functional studies, we propose a potential genotype-phenotype correlation, with a greater reduction in protein expression being associated with a more severe phenotype.Taken together, our findings broaden the known phenotypic and molecular spectrum and emphasize that NHLRC2-related disease should be considered in patients presenting with intellectual disability, movement disorders, neuroregression and epilepsy with or without pulmonary involvement.

Novel Biomarkers Aim at Detecting Metastatic Sentinel Lymph Nodes in Breast Cancer

Background: Intra-operative molecular diagnostic assays are currently used for the detection of lymph node metastases. The objective of this study was to find new biomarkers to improve diagnostic accuracy in the detection of metastatic axillary lymph nodes in breast cancer patients. Methods: We applied an absolute quantitative real-time reverse transcription-PCR to quantitate the expression of CK19, KLK11, and CLEC3A mRNAs in 79 FFPE sentinel lymph nodes (SLNs) from 35 breast cancer patients. The CK19 was confirmed as a standard biomarker, and the level of expression of selected new markers, KLK11 and CLEC3A, was evaluated in pathologically negative and positive SLNs by using absolute quantitative real-time PCR. Results: The overall concordance of the CK19 gene with pathological results was 92.4% (less than 250 copies) in negative SLNs and 85% in positive SLNs (more than 250 copies). The sensitivity and specificity of CK19, which were detected by real-time PCR, was 85% and 46%, respectively. Our results revealed that lower CLEC3A was associated with more lymph node involvement. We could set a cut-off point for CLEC3A with the sensitivity of 78% and specificity of 60%. Also, the mean KLK11 had a statistically significant reverse correlation with tumor grade (p = 0.017). Higher CK19 levels were related to more tumor invasion (p < 0.0001). Conclusion: Regarding the findings, CLEC3A along with CK19 can be used as a promising marker with high sensitivity and specificity for the detection of metastatic SLN.

Early pyeloplasty versus conservative management of severe ureteropelvic junction obstruction in asymptomatic infants.

BACKGROUND: Ureteric-pelvic junction obstruction (UPJO) is the most common cause of antenatal and neonatal hydronephrosis and its management remains controversial. While conservative management is advocated for all, this strategy puts a quarter of these patients at risk for possibly irreversible renal damage. AIM: In this study, we compare functional and anatomic outcomes in newborns and infants less than 1 year of age with high-grade unilateral UPJO, following early surgical pyeloplasty (ESP) versus conservative management (CM). MATERIALS AND METHODS: This was a single center prospective interventional study. Infants referred to our tertiary care pediatric surgery clinic between September 2016 and September 2018 with UPJO were considered. To be included patients must have been less than 1 year old, lack of clinical symptoms, suffer from severe hydronephrosis as defined by Society for Fetal Urology (SFU) grades 3 or 4, and have affected kidney Split Renal Function (SRF) above 40%. Patients with bilateral disease, structural anomalies, or an abnormal voiding cystourethrogram (VCUG) were excluded. Anatomical and functional outcomes were measured and compared at 6 and 12 months. RESULTS: Fifty-six patients were assigned to receive either ESP (n = 28) or CM (n = 28). At 6 months Cortical thickness, polar length, and SFU indices were significantly lower in the ESP group, while none of the outcomes were significantly different between the two groups at 12 months. Despite the two groups not being different at 12 months regarding differential renal function (DRF), there was a significant decrease of function in the CM group compared to baseline. CONCLUSION: When considering treatment options for infants with high-grade UPJO, it appears that ESP hastens improvement of anatomic and functional indices, while CM may lead to a significant deterioration in renal function.