Objective: To identify novel candidate diagnostic microRNA (miRNA) markers of endometriosis by means of an unbiased search with confirmation by means of targeted polymerase chain reaction (PCR). Design: Retrospective cohort. Setting: University teaching hospitals. Patient(s): Women with endometriosis and control women, confirmed with the use of laparoscopy. Interventions(s): Diagnostic laparoscopy and blood sample. Main Outcome Measure(s): Next-generation sequencing (NGS) and quantitative real-time PCR (qRT-PCR).Result(s): Candidate miRNAs differentially expressed in women with endometriosis compared with control women were identified by means of NGS and selected for qRT-PCR. Plasma samples from another cohort of women with surgically confirmed endometriosis (n ¼ 53) and disease-free control women (n ¼ 53) were checked for hemolysis using spectrophotometry and the ratio of miR-23a and miR-451 by means of qRT-PCR. MicroRNA signatures were quantified by means of qRT-PCR in hemolysis-free plasma samples of case subjects (n ¼ 25) and control subjects (n ¼ 28) with the use of miRcury LNA miRNA. Circulating levels of eight miRNAs (miR-199a-3p, miR-143-3p, miR-340-5p, let-7b-5p, miR-21-5p, miR-17-5p, miR-20a-5p, and miR-103a-3p) were significantly lower in case subjects compared to control subjects. The sensitivity and specificity for individual miRNAs ranged from 0.36 to 1.00 and from 0.43 to 1.00, respectively, but when combined produced sensitivity and specificity of 0.92 and 0.86 with positive (PPV) and (NPV) predictive values of 0.85 and 0.92, respectively. However, combination of five miRNAs (miR-17-5p, miR-20a-5p, miR-199a-3p, miR-143-3p, and let-7b-5p) produced sensitivity and specificity of 0.96 and 0.79 with PPV and NPV of 0.80 and 0.96, respectively. Conclusion(s):We conclude that a panel of candidate miRNAs was comparable to laparoscopy in distinguishing between women with endometriosis and control women. (Fertil Steril Ò 2020;113:1232-41. Ó2020 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

In the context of a comprehensive research project, investigating novel autosomal recessive intellectual disability (ARID) genes, linkage analysis based on autozygosity mapping helped identify an intellectual disability locus on Chr.12q24, in an Iranian family (LOD score ¼ 3.7). Next-generation sequencing (NGS) following exon enrichment in this novel interval, detected a nonsense mutation (p.Q1010*) in the CLIP1 gene. CLIP1 encodes a member of microtubule (MT) plus-end tracking proteins, which specifically associates with the ends of growing MTs. These proteins regulate MT dynamic behavior and are important for MT-mediated transport over the length of axons and dendrites. As such, CLIP1 may have a role in neuronal development. We studied lymphoblastoid and skin fibroblast cell lines established from healthy and affected patients. RT-PCR and western blot analyses showed the absence of CLIP1 transcript and protein in lymphoblastoid cells derived from affected patients. Furthermore, immunofluorescence analyses showed MT plus-end staining only in fibroblasts containing the wild-type (and not the mutant) CLIP1 protein. Collectively, our data suggest that defects in CLIP1 may lead to ARID.

Upon revisiting their published work on a defect in the CLIP1 gene, the authors noted that the brain MRI obtained from the affected girl (IV: 7), which was reported to be normal at that time, showed a local white matter around fornices with abnormal signal of the frontal horns' 'focal leukoencephalopathy'. They would like to report focal leukodystrophy in the brain MRI of the patient with CLIP1 mutation as a migration role of this gene in cortical neurons (Figure 1). Figure 1 (a) Axial section of flair showed local white matter around fornices with abnormal signal of frontal horns 'focal leukodystrophy'.