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Returning to the composition associated with autonomously burning patterns inside Yarrowia lipolytica and its function in pathway executive.
Conclusion The patient's condition may be attributed to the novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene.Objective To explore the clinical features and genetic basis for a patient with hereditary hypophosphatemic rickets with hypercalciuria(HHRH). Methods Clinical data of the patient was collected. The patient was subjected to whole exome capture and next generation sequencing (NGS). Suspected variants were verified by Sanger sequencing. Results The patient presented with hypophosphatemic rickets, short stature, hypercalciuria, and renal stones. NGS showed that he has carried compound heterozygous variants of the SLC34A3 gene, namely c.532_533delCA(p.Q178Vfs*6) and c.894_925+69del(splicing). His parents were asymptomatic heterozygous carriers of one of the variants. Based on ACMG guidelines, both variants were classified as pathogenic. Conclusion The compound heterozygous variants c.532_533delCA (p.Q178Vfs*6) and c.894_925+69del(splicing) of the SLC34A3 gene probably underlie the disease in this child. Above finding has enriched the variant spectrum for HHRH. Based on the results, prenatal diagnosis may be provided for the family.Objective To explore the molecular basis for a Chinese pedigree affected with hereditary coagulation factor VII (FVII) deficiency. Methods The coding regions of F7 gene were amplified by PCR and sequenced. Suspected variants were confirmed by reverse sequencing and validated in other members from the pedigree. Pathogenicity of the variants was analyzed with multiple bioinformatic tools. Results Genetic analysis revealed that the proband has carried compound heterozygous c.985T>C (p.Ser329Pro) and c.1091G>A (p.Arg364Gln) variants in exon 8 of the F7 gene. Her mother, brother and son were heterozygous for c.985T>C (p.Ser329Pro), while her father was heterozygous for c.1091G>A (p.Arg364Gln). Phylogenetic analysis suggested that both p.Ser329 and p.Arg364 are highly conserved among homologous species. Online bioinformatic software predicted both variants to be deleterious. Protein model analysis suggested that the Pro329 side chain may form a new hydrogen bond with Leu333. The Pro benzene ring may clash with Glu325 in the p.Ser329Pro variant model. The p.Arg364Gln variant have two additional hydrogen bonds compared with wild type Arg364. Lonafarnib inhibitor Both variants may lead to alteration of the protein structure. Conclusion The p.Ser329Pro and p.Arg364Gln variants in exon 8 of the F7 gene probably account for the reduced FVII in this pedigree.Objective To report on echocardiographic finding and genetic testing of three fetuses with cardiac rhabdomyoma. Methods Clinical data of the three fetuses was collected. High-throughput sequencing was carried out to analyze the whole exomes of the three fetuses. Suspected variants were confirmed by Sanger sequencing. Results Multiple hyperechoic masses were found in both ventricles of the three fetuses, suggesting the presence of fetal cardiac rhabdomyoma. Genetic testing revealed that fetus 1 carried a heterozygous c.740G>A (p.W247*) variant of the TSC1 gene, fetus 2 carried a previously known heterozygous c.3352C>T (p.Q1118*) variant of the TSC2 gene. Fetus 3 carried a previously known heterozygous c.1579C>T (p.Q527*) variant of the TSC1 gene. None of their parents carried the same variant. Literature review has identified 109 fetuses with relatively complete data. Cardiac rhabdomyomas in ventricles and ventricular septum was reported in 89, and multiple cardiac rhabdomyoma was reported in 79. Out of the 94 cases who underwent genetic testing, 74 have carried variants of the TSC1 or TSC2 genes. Conclusion Fetal cardiac rhabdomyoma may present as multiple hyperechoic intraventricular masses. Most of them are associated with other manifestation of tuberous sclerosis. Such cases may warrant prenatal genetic testing.Objective To assess the value of non-invasive prenatal testing (NIPT) for the identification of sex chromosome aneuploidies (SCAs), copy number variants (CNVs) and rare autosomal trisomies (RATs). Methods A total of 11 429 women with singleton pregnancy in Ningbo area were screened by NIPT. 106 women were subjected to invasive prenatal diagnosis due to high risk of chromosomal abnormalities other than 21, 18 and 13 aneuploidies. All cases were followed up for pregnancy outcome and postnatal status. Results Sixty-six women were signaled by NIPT for fetal SCAs, among whom 54 were willing to undergo prenatal diagnosis. Eighteen cases of fetal SCAs were verified as true positives and 4 were suspected positives, which yielded a positive predictive value (PPV) of 33.3%. Half of the women decided to continue their pregnancy. Forty women were signaled by NIPT for fetal CNVs, among which 32 underwent prenatal diagnosis. 19 cases of fetal CNVs were verified as true positives and 3 cases were suspected positives, which yielded a PPV of 46.8%. All women with pathological or possibly pathological CNVs decided to terminate their pregnancies. Thirty-one women were signaled for with fetal RATs. Two fetuses were confirmed to harbor mosaicism trisomies by prenatal diagnosis, and 1 case was suspected to be positive, which yielded a PPV of 9.7%. All of the three women have decided to terminate their pregnancy. Conclusion In addition to aneuploidies of target chromosomes, NIPT also has important value for the detection of SCAs and CNVs. The results can help to further reduce birth defects. Nevertheless, in view of its low PPV, pregnant women with positive result still need appropriate genetic counseling and prenatal diagnosis to avoid unnecessary induced labor.Objective To study the influence of maternal sex chromosomal abnormalities on the prediction of fetal sex chromosome abnormalities (SCAs) by non-invasive prenatal testing (NIPT). Methods Thirty-six pregnant women with a prediction for fetal SCAs by NIPT were verified as false positive after prenatal diagnosis using amniotic fluid samples. With informed consent, these women were subjected to chromosomal karyotyping or copy number variations (CNVs) analysis through high-throughput sequencing. Results Sex chromosomal abnormalities were found in 8 women, which yielded an abnormal rate of 22.22% (8/36). Among these, 3 had sex chromosome aneuploidies (47, XXX), 4 had sex chromosome mosaicisms, and 1 carried structural chromosomal abnormalities. Reanalysis of the results of NIPT were consistent with the maternal CNVs by large. With the ratio of cffDNA (ChrX)/cffDNA was more than 2, 6 of the eight women were found to harbor sex chromosome abnormalities, and the fetal karyotype was normal. However, with a ratio of less than 2, only 2 of the 38 pregnant women had sex chromosome abnormalities, and 10 of the fetuses were confirmed as positive.
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