Cockayne syndrome is an autosomal recessive multisystem disorder characterized principally by neurological and sensory impairment, cachectic dwarfism, and photosensitivity. This rare disease is linked to mutations in the CSB/ERCC6 and CSA/ERCC8 genes encoding proteins involved in the transcription-coupled DNA repair pathway. The clinical spectrum of Cockayne syndrome encompasses a wide range of severity from severe prenatal forms to mild and late-onset presentations. We have reviewed the 45 published mutations in CSA and CSB to date and we report 43 new mutations in these genes together with the corresponding clinical data. Among the 84 reported kindreds, 52 (62%) have mutations in the CSB gene. Many types of mutations are scattered along the whole coding sequence of both genes, but clusters of missense mutations can be recognized and highlight the role of particular motifs in the proteins. Genotype-phenotype correlation hypotheses are considered with regard to these new molecular and clinical data. Additional cases of molecular prenatal diagnosis are reported and the strategy for prenatal testing is discussed. Two web-based locus-specific databases have been created to list all identified variants and to allow the inclusion of future reports (www.umd.be/ CSA/ and www.umd.be/CSB/). Hum Mutat 31:113-126,

Infertility concerns a minimum of 70 million couples worldwide. An important proportion of cases is believed to have a genetic component, yet few causal genes have been identified so far. In a previous study, we demonstrated that a homozygous mutation (c.144delC) in the Aurora Kinase C (AURKC) gene led to the production of large-headed polyploid multi-flagellar spermatozoa, a primary infertility phenotype mainly observed in North Africans. We now want to estimate the prevalence of the defect, to improve our understanding of AURKC physiopathology in spermatogenesis and assess its implication in oogenesis. A carrier frequency of 1/50 was established from individuals from the Maghrebian general population, comparable to that of Y-microdeletions, thus far the only known recurrent genetic event altering spermatogenesis. A total of 62 patients were genotyped, all who had a typical phenotype with close to 100% large-headed spermatozoa were homozygously mutated (n = 32), whereas no AURKC mutations were detected in the others. Two homozygous females were identified; both were fertile indicating that AURKC is not indispensible in oogenesis. Previous FISH results had showed a great chromosomal heterogeneity in these patient's spermatozoa. We demonstrate here by flow cytometry that all spermatozoa have in fact a homogeneous 4C DNA content and are thus all blocked before the first meiotic division. Our data thus indicate that a functional AURKC protein is necessary for male meiotic cytokinesis while its absence does not impair oogenesis.

These results indicate that hyper-methylation in testis DNA from NOA patients is specific and not due a general methylation defect, and suggest that epigenetic silencing of MTHFR could play a role in azoospermic infertility.

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.

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