Efficacy and initial clinical evaluation of optical genome mapping in the diagnosis of structural variations / 中华预防医学杂志

To investigate the efficacy and value of optical genome mapping (OGM) in detecting chromosomal structural variations. In a clinical study about high-precision analysis of genomic structural variation for complex genetic diseases, a retrospective study was performed on the cases with karyotyping at the department of Obstetrics and Gynecology, and Endocrinology of Peking Union Medical College Hospital from January to December 2021. Ten cases with abnormal karyotype was detected by OGM. Partial cases were verified by fluorescence in situ hybridization (FISH), SNP array or CNV-seq. Results of ten cases, nine were detected with abnormality by OGM, including unbalanced chromosomal rearrangements (n=3), translocation (n=5) and paracentric inversion (n=1), and the results were in concordance with other standard assays. However, one case with breakpoint and reconnected at centromere has not been detected. In conclusion, ten samples were comprehensively analyzed by karyotyping, FISH, SNP array or CNV-seq, and OGM, and results demonstrated that optical genome mapping as a new technology can not only detect unbalanced rearrangements such as copy number variants as well as balanced translocations and inversions, but more importantly, it can refine breakpoints and orientation of duplicated segments or insertions. So it can contribute to the diagnosis of genetic diseases and prevent birth defect. However, the current technology is not yet capable of detecting breakpoints of balanced structural variations lying within unmapped regions.

Genetic counseling, prenatal screening and diagnosis of Down syndrome in the second trimester in women of advanced maternal age: a prospective study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The incidence of autosomal trisomy in livebirths is strongly dependent on maternal age. Special consideration is given to the provision of prenatal screening and cytogenetic testing to women of advanced maternal age (AMA). The aim of this study was to evaluate the effectiveness of second trimester prenatal screening and amniocentesis for Down syndrome (DS) and compare the trends of choice of screening and amniocentesis among AMA women.</p><p><b>METHODS</b>A total of 5404 AMA patients with natural singleton pregnancy were recruited for this prospective study from January 2008 to December 2010. The gestational weeks were from 15 weeks to 20(+6) weeks. The patients referred were grouped into a screening group (2107 cases) and an amniocentesis group (3297 cases) by their own decision. The prevalence of DS was compared between the two groups by chi-square test. Choice rates for each maternal age with trends were compared by regression analysis.</p><p><b>RESULTS</b>There were 18 cases of fetal DS detected in the screening group with a prevalence of 8.54‰ (18/2107). Twenty-five cases of fetal DS were diagnosed in the amniocentesis group with a prevalence of 7.58‰ (25/3297). No statistical difference was observed in the prevalence of DS between the screening and amniocentesis group (P = 0.928). The invasive testing rate for DS in the amniocentesis group was 5.54 times higher than that of the screening group (1/131.88 vs. 1/23.78). With the increase of the maternal age, the choice of amniocentesis increased while the choice of the screening showed an opposite trend. The choice of the AMA women between the screening and amniocentesis was significantly age relevant (P = 0.012).</p><p><b>CONCLUSIONS</b>The second trimester serum screening in combination with maternal age was more effective than maternal age alone to screen for DS. We suggest educating the patients by recommending AMA women be informed of both screening and amniocentesis options.</p>

Prenatal diagnosis for hereditary deaf families assisted by genetic testing / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To provide prenatal diagnosis for deaf families, which the first child was confirmed to be hereditary deafness caused by gap junction beta-2 (GJB2) or SLC26A4 (PDS) mutation, to avoid another deaf birth in these families.</p><p><b>METHODS</b>Eight deaf families joined in this study. Each family had one child with severe to profound hearing loss while parents had normal hearing except a deaf father from family 8; mothers had been pregnant for 6-28 weeks. Genetic testing of GJB2, SLC26A4 and mitochondrial DNA (mtDNA) A1555G mutation were firstly performed in probands and their parents whose DNA was extracted from peripheral blood, and then prenatal testing was carried out in the fetus whose DNA was extracted from different fetus materials depending on the time of gestation.</p><p><b>RESULTS</b>The probands from family 1-4 were found to carry homozygous or compound GJB2 mutations while their parents carried corresponding heterozygous GJB2 mutations. The probands from family 5-8 and the deaf father from family 8 were found to carry compound SLC26A4 mutations while their parents and the mother from family 8 carried a single SLC26A4 mutation. Prenatal testing showed that the fetuses from family 1, 5, 8 only carried the paternal mutation and the fetuses from family 2, 3, 6 didn't carry any GJB2 or SLC26A4 mutations. The new born babies from these six families all had normal hearing revealed by new born hearing screening. However, the fetuses from family 4,7 carried the same mutations with probands in each family. The parents from family 4, 7 decide to terminate pregnancy.</p><p><b>CONCLUSION</b>Prenatal diagnosis assisted by genetic testing can provide efficient information about hearing condition of their offsprings.</p>

Postnatal and prenatal diagnosis of mucopolysaccharidosis type II (Hunter syndrome) / 中华儿科杂志

<p><b>OBJECTIVE</b>Mucopolysaccharidosis type II (MPS II, Hunter syndrome, OMIM 309900) is an X-linked recessive lysosomal storage disease resulting from a deficiency of iduronte-2-sulphate sulphatase (IDS). The present study aimed to establish an enzyme assay method for IDS activity for carrying out postnatal and prenatal diagnosis of MPS II by means of IDS activity assay on plasma, uncultured chorionic villi (CV) and cultured amniotic fluid cells (AF cell) using a new synthesized substrate.</p><p><b>METHODS</b>A fluorigenic substrate (4-methylumbelliferyl-alpha-iduronate-2-sulphate, MU-alpha-Idu-2S) was used for the assay of IDS activity. IDS activity in plasma was determined for diagnosis of the proband. Prenatal diagnosis in 10 pregnancies at risk was carried out according to IDS activity on uncultured CV at 11th week or on cultured AF cell at 18th week of gestation. At the same time, IDS activity was also determined in the maternal plasmas to observe the change of IDS activity in pregnancy. The fetal sex determination was performed by PCR amplification of the ZFX/ZFY genes.</p><p><b>RESULT</b>The IDS activity in plasma of normal controls and obligate heterozygotes were 240.2 - 668.2 nmol/(4 hxml) and 88.7 - 547.9 nmol/(4 hxml), respectively, while the enzyme activities in plasmas were in the range of 0.3 - 18.6 nmol/(4 hxml) in affected male. The IDS activities were 37.2 - 54.9 nmol/(4 hxmg protein) and 21.4 - 74.4 nmol/(4 hxmg protein) in CV and cultured AF cells respectively. Out of 50 suspected cases, 46 were diagnosed as having MPS II and 4 were excluded. Prenatal diagnosis was performed on 10 pregnancies at risk. Four of 5 male fetuses [IDS activity were 4.7, 1.8, 7.0 nmol/(4hxmg protein) in CV, 0.6 nmol/(4 hxmg protein) in AF cell] were diagnosed as having MPS II and the other 5 fetuses were normal females [IDS activity were: 48.7, 5.9, 25.2 nmol/(4 hxmg protein) in CV, 55.2, 40.9 nmol/(4 hxmg protein) in AF cell]. Increased IDS activity was observed in plasma of the pregnant women with unaffected fetuses, while the IDS activity decreased in pregnancies with affected fetuses. IDS activity of one female fetus was very low [5.9 nmol/(4 hxmg protein)], but the IDS activity in maternal plasmas increased, this fetus was a normal female.</p><p><b>CONCLUSIONS</b>The method using a synthesized fluorigenic 4-methylumbelliferyl-substrate was a sensitive, rapid and convenient assay of IDS activity and was reliable for early prenatal diagnosis. Determination of fetal sex would be helpful in excluding the female fetus with low IDS activity from being considered as an affected male fetus. It would be further helpful if IDS activity in maternal plasma was taken into account.</p>

Detection of the gene-deleted female carriers of Duchenne/Becker muscular dystrophy using a fluorescent in situ hybridization based method / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To set up a fluorescent in situ hybridization (FISH) based method to detect the gene-deleted female carriers of Duchenne/Becker muscular dystrophy (DMD/BMD).</p><p><b>METHODS</b>Multiplex polymerase chain reaction was used to identify the gene deletion DMD/BMD probands and their female relatives were checked by double-color FISH.</p><p><b>RESULTS</b>Two probands whose exon 46 of dystrophin gene was deleted, one had a positive pedigree and the other was a sporatic patient. In the case of the positive pedigree, four carriers were detected. In the case of the sporatic family, FISH showed that the mother of the proband was a somatic mosaicism.</p><p><b>CONCLUSION</b>Combined with multiplex PCR, double-color FISH is a simple, fast, directly visual and accurate method. It is feasible to identify the carrier status of the female relatives of the gene deletion DMD/BMD probands. The detection of the somatic mosaicism is a prominent feature of FISH.</p>

Study on the correlation of serum folate and red blood cell folate level with birth defects and unexplained recurrent pregnancy loss / 中华妇产科杂志

0.05). The RBC folate level of birth defect group except the urinary defect was significantly lower compared with the control group(233-547 vs 689 nmol/L,P