Meckel syndrome (MKS) is a pre-or perinatal multisystemic ciliopathic lethal disorder with an autosomal recessive mode of inheritance. Meckel syndrome is usually manifested with meningo-occipital encephalocele, polycystic kidney dysplasia, postaxial polydactyly and hepatobiliary ductal plate malformation. Germline variants in CEP290 cause MKS4. In this study, we investigated a 35-years-old Chinese female who was 17+1 weeks pregnant. She had a history of adverse pregnancy of having foetus with multiple malformations. We performed ultrasonography and identified the foetus with occipital meningoencephalocele and enlarged cystic dysplastic kidneys. So, she decided to terminate her pregnancy and further genetic molecular analysis was performed. We identified the aborted foetus without postaxial polydactyly. Histological examination of foetal kidney showed cysts in kidney and thinning of the renal cortex with glomerular atrophy. Whole exome sequencing identified a novel homozygous variant (c.2144T>G; p.L715 * ) in exon 21 of the CEP290 in the foetus. Sanger sequencing confirmed that both the parents of the foetus were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters of the foetus as well as in the 100 healthy individuals. Western blot analysis showed that this variant leads to the formation of truncated CEP290 protein with the molecular weight of 84 KD compared with the wild-type CEP290 protein of 290 KD. Hence, it is a loss-of-function variant.We also found that the mutant cilium appears longer in length than the wild-type cilium. Our present study reported the first variant of CEP290 associated with MKS4 in Chinese population.

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Inflammation and immunity are thought as risk factors for uterine leiomyoma; however, detailed reports on this topic are scarce. The present study aimed to analyze the characteristics of immune function and clinical significance of circulating CD4/CD8 T, NK, and γδ T cells in reproductive females with uterine leiomyoma. We analyzed the above-mentioned cells in 30 reproductive females with uterine leiomyoma and 68 healthy females using flow cytometry. After that, the correlation between function of immune cells and clinical phenotypes was analyzed. Compared with healthy controls, central memory (CM) CD4/CD8 T cells as well as Treg and Tfh cells were notably increased in leiomyoma patients; however, NK and γδ T cells were decreased in patients. Moreover, such alterations of these cells in patients with leiomyoma were associated with shorter menstrual cycles, longer menstrual period, anemia, pelvic lesions, more and larger myomas, and higher levels of CA125. Additionally, the increased Tfh1/Tfh2 ratio and Tfh17 were significantly associated with longer menstrual period, more myomas, and higher CA125 levels independent of age in patients with uterine leiomyoma. In conclusion, hallmarks of peripheral immune function are remarkably correlated with clinical phenotypes in reproductive females with uterine leiomyoma. This preliminary work may provide proof-of-concept for evaluating efficacy of treatment and prognosis of reproductive females with uterine leiomyoma with the help of quantitative analysis of peripheral immune function, which may inspire performing further investigations on the relevance of immune function with different diseases.

XPG gene contributes to DNA repair defects and genomic instability, which may lead to the initiation of uterine leiomyoma. We hypothesized that genetic variants of XPG gene may alter the carriers’ susceptibility to leiomyoma. The association between five potential functional single nucleotide polymorphisms (SNPs), i.e. rs2094258 C>T, rs751402 C>T, rs2296147 T>C, rs1047768 T>C, rs873601 G>A, and uterine leiomyoma risk in Chinese, was investigated in this case–control study, which included 398 incident leiomyoma cases and 733 controls. We found that rs873601 was significantly associated with tumor risk in a recessive genetic model after being adjusting for age and menopause. When compared with rs873601 GG/GA genotypes, the AA genotype had an increased leiomyoma risk (adjusted OR = 1.59, 95% CI = 1.16–2.18, P=0.004; Bonferroni adjusted P=0.040). Furthermore, stratified analysis revealed that the association between the rs873601 AA genotype and leiomyoma risk was more evident among subjects younger than 40 years old (adjusted OR = 1.58, 95% CI = 1.06–2.35, P=0.023) and patients who had more than three myomas (adjusted OR = 2.05, 95% CI = 1.24–3.41, P=0.006). Yet, no significant association between the other four polymorphisms and leiomyoma risk was observed. To sum up, the present study reported on the association between XPG gene polymorphisms and myoma risk. The observed data indicated that SNP rs873601 G>A contributes to uterine leiomyoma susceptibility in a Southern Chinese population.