An unusual case of trisomy 8 mosaicism complicated by coexistence of phenylketonuria.

Trisomy 8 syndrome, also known as " Warkany syndrome type 2 ", was first reported in 1971. Complete trisomy 8 are mostly aborted spontaneouslyinthe first trimester. Trisomy 8 mosaicism (T8M), predominated in the current cases reported. Itisahighlyheterogeneous Chromosome disorder. We know little about its effects on fertility. In this case, a patient with T8M combined with phenylketonuria was diagnosed. She's mentally retarded. After evaluating the anatomy and function of the reproductive system, the patient conceived through preimplantationgenetictesting-intracytoplasmicsperminjection-embryotransfer (PGT-ICSI-ET) and obtained a healthy fetus, which is the first report. The study focuses on the maintenance of fertility in patients with T8M, the effects of phenylketonuria and genetic counseling.

Application of Copy Number Variation Sequencing Technology in 422 Foetuses with Abnormal Ultrasound Soft Markers.

Purpose: The application value of ultrasound soft indicators in prenatal diagnosis was evaluated by copy number variation sequencing (CNV-seq). Methods: The authors conducted a retrospective analysis of 422 pregnant women who underwent CNV-seq testing at Luoyang Maternal and Child Health Hospital between January 2020 and November 2021. The women had presented with abnormal ultrasound soft markers; those identified as high-risk through non-invasive prenatal screening were excluded. Results: A total of 43 abnormal cases were detected in 422 pregnant women, including 24 aneuploidy (including chimerism) and 19 pathogenic or likely pathogenic copy number variations (CNVs). Based on the characteristics of ultrasound soft indicators, pregnant women were divided into five groups: isolated nuchal translucency (NT) group, combined NT group, isolated soft indicators group, combined soft indicators group and combined non-NT group. The abnormality detection rates in the five groups were 12.38% (13/105), 36.11% (13/36), 3.74% (4/103), 3.08% (2/63) and 10.09% (11/109), respectively. Statistical tests showed that the detection rate in the NT thickening combined with other abnormalities group was significantly higher than the other four groups, while there was no statistical difference in the detection rate among the other four groups. Conclusion: When NT thickening is combined with other abnormalities, it is more likely to indicate chromosome abnormalities or CNVs, so it should be regarded seriously upon finding, and pregnant women should be referred for prenatal diagnosis according to the examination results. In addition, NT thickening is an important indicator for prenatal diagnosis and should be considered regardless of whether it occurs independently. The authors recommend CNV-seq for prenatal diagnosis to prevent missing small fragments of CNVs during traditional karyotyping.

Cat eye syndrome caused by 22q11.1q11.21 duplication: case report in a Chinese family.

PURPOSE:  This paper presents a report on two uncommon instances of cat eye syndrome in a Chinese family. CASE PRESENTATION: The proband, a 23-year-old female, exhibited a diminutive cornea and complete blindness in her right eye, and the uncorrected distance visual acuity of her left eye was 0.7 LogMAR. Peripheral blood chromosome karyotyping reveal a karyotype of 47, XX, + mar. Subsequent analysis of chromosome copy number variation unveiled a 1.5 Mb duplication in the 22q11.1q11.21 region of the proband. The proband's mother,aged 49, displayed small eyes, wide-set eyes, downward slanting eyelids, and congenital heart disease. Chromosome copy number variation analysis also showed a 1.55 Mb duplication in the 22q11.1q11.21 region of chromosome 22 in the proband's mother. Ultimately, both members of this family were diagnosed with cat eye syndrome. CONCLUSION:  Cat eye syndrome is a rare genetic disorder that greatly affects patients' lives and requires personalized treatment. This study provides new evidence for a better understanding of the diagnosis of cat eye syndrome and emphasizes the importance of genetic counseling and supervision.

A novel variant of the SOX10 gene associated with Waardenburg syndrome type IV.

BACKGROUND: Waardenburg syndrome (WS) is a rare genetic disorder characterized by varying degrees of sensorineural hearing loss and accumulated pigmentation in the skin, hair and iris. The syndrome is classified into four types (WS1, WS2, WS3, and WS4), each with different clinical phenotypes and underlying genetic causes. The aim of this study was to identify the pathogenic variant in a Chinese family with Waardenburg syndrome type IV. METHODS: The patient and his parents underwent a thorough medical examination. We applied whole exome sequencing to identify the causal variant on the patient and other family members. RESULTS: The patient presented with iris pigmentary abnormality, congenital megacolon and sensorineural hearing loss. The clinical diagnosis of the patient was WS4. The whole exome sequencing (WES) revealed a novel variant (c.452_456dup) in the SOX10 gene, which could be responsible for the observed pathogenic of WS4 in this patient. Our analysis suggests that this variant produces a truncated protein that contributes to the development of the disease. The genetic test confirmed the diagnosis of WS4 in the patient from the studied pedigree. CONCLUSIONS: This present study demonstrated that genetic test based on WES, an effective alternative to regular clinical examinations, helps diagnose WS4. The newly identified SOX10 gene variant can expand the understanding of WS4.

Prenatal diagnosis of fetuses with ultrasound anomalies by whole-exome sequencing in Luoyang city, China.

Background: There is a great obstacle in prenatal diagnosis of fetal anomalies due to their considerable genetic and clinical heterogeneity. Whole-exome sequencing (WES) has been confirmed as a successful option for genetic diagnosis in pediatrics, but its clinical utility for prenatal diagnosis remains to be limited. Methods: A total of 60 fetuses with abnormal ultrasound findings underwent karyotyping or chromosomal microarray analysis (CMA), and those with negative results were further subjected to WES. The identified variants were classified as pathogenic or likely pathogenic (P/LP) and the variant of uncertain significance (VUS). Pregnancy outcomes were obtained through a telephone follow-up. Results: Twelve (20%, 12/60) fetuses were diagnosed to have chromosomal abnormalities using karyotyping or CMA. Of the remaining 48 cases that underwent WES, P/LP variants were identified in 14 cases (29.2%), giving an additional diagnostic yield of 23.3% (14/60). The most frequently affected organ referred for prenatal WES was the head or neck system (40%), followed by the skeletal system (39.1%). In terms of pathogenic genes, FGFR3 was the most common diagnostic gene in this cohort. For the first time, we discovered five P/LP variants involved in SEC24D, FIG4, CTNNA3, EPG5, and PKD2. In addition, we identified three VUSes that had been reported previously. Outcomes of pregnancy were available for 54 cases, of which 24 cases were terminated. Conclusion: The results confirmed that WES is a powerful tool in prenatal diagnosis, especially for fetuses with ultrasonographic anomalies that cannot be diagnosed using conventional prenatal methods. Additionally, newly identified variants will expand the phenotypic spectrum of monogenic disorders and greatly enrich the prenatal diagnostic database.

Association of Clinical and Immunological Characteristics With Disease Severity and Outcomes in 211 Patients With COVID-19 in Wuhan, China.

Background: Coronavirus disease 2019 (COVID-19) has posed a great threat to global public health. There remains an urgent need to address the clinical significance of laboratory finding changes in predicting disease progression in COVID-19 patients. We aimed to analyze the clinical and immunological features of severe and critically severe patients with COVID-19 in comparison with non-severe patients and identify risk factors for disease severity and clinical outcome in COVID-19 patients. Methods: The consecutive records of 211 patients with COVID-19 who were admitted to Zhongnan Hospital of Wuhan University from December 2019 to February 2020 were retrospectively reviewed. Results: Of the 211 patients with COVID-19 recruited, 111 patients were classified as non-severe, 59 as severe, and 41 as critically severe cases. The median age was obviously higher in severe and critically severe cases than in non-severe cases. Severe and critically severe patients showed more underlying comorbidities than non-severe patients. Fever was the predominant presenting symptom in COVID-19 patients, and the duration of fever was longer in critically severe patients. Moreover, patients with increased levels of serum aminotransferases and creatinine (CREA) were at a higher risk for severe and critical COVID-19 presentations. The serum levels of IL-6 in severe and critically severe patients were remarkably higher than in non-severe patients. Lymphopenia was more pronounced in severe and critically severe patients compared with non-severe patients. Lymphocyte subset analysis indicated that severe and critically severe patients had significantly decreased count of lymphocyte subpopulations, such as CD4+ T cells, CD8+ T cells and B cells. A multivariate logistic analysis indicated that older age, male sex, the length of hospital stay, body temperature before admission, comorbidities, higher white blood cell (WBC) counts, lower lymphocyte counts, and increased levels of IL-6 were significantly associated with predicting the progression to severe stage of COVID-19. Conclusion: Older age, male sex, underlying illness, sustained fever status, abnormal liver and renal functions, excessive expression of IL-6, lymphopenia, and selective loss of peripheral lymphocyte subsets were related to disease deterioration and clinical outcome in COVID-19 patients. This study would provide clinicians with valuable information for risk evaluation and effective interventions for COVID-19.

Overexpression of HvHGGT Enhances Tocotrienol Levels and Antioxidant Activity in Barley.

Vitamin E is a potent lipid-soluble antioxidant and essential nutrient for human health. Tocotrienols are the major form of vitamin E in seeds of most monocots. It has been known that homogentisate geranylgeranyl transferase (HGGT) catalyzes the committed step of tocotrienol biosynthesis. In the present study, we generated transgenic barley overexpressing HvHGGT under endogenous D-Hordein promoter (proHor). Overexpression of HvHGGT increased seed size and seed weight in transgenic barley. Notably, total tocotrienol content increased by 10-15% in seeds of transgenic lines, due to the increased levels of δ-, ß-, and γ-tocotrienol, but not α-tocotrienol. Total tocopherol content decreased by 14-18% in transgenic lines, compared to wild type. The antioxidant activity of seeds was determined by using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), and lipid peroxidation assays. Compared to wild type, radical scavenging activity of seed extracts was enhanced by 17-18% in transgenic lines. Meanwhile, the lipid peroxidation level was decreased by about 20% in transgenic barley seeds. Taken together, overexpression of HvHGGT enhanced the tocotrienol levels and antioxidant capacity in barley seeds.

Over-expression of (1,3;1,4)-ß-D-glucanase isoenzyme EII gene results in decreased (1,3;1,4)-ß-D-glucan content and increased starch level in barley grains.

BACKGROUND: High content of (1,3;1,4)-ß-d-glucan in barley grains is regarded as an undesirable factor affecting malting potential, brewing yield and feed utilization. Production of thermostable bacterial (1,3;1,4)-ß-glucanase in transgenic barley grain or supplementation of exogenous bacterial (1,3;1,4)-ß-glucanase has been used to improve malt and feed quality. The aim of the present study was to investigate the effect of over-expression of an endogenous (1,3;1,4)-ß-glucanase on ß-glucan content and grain composition in barley. RESULTS: A construct containing full-length HvGlb2 cDNA encoding barley (1,3;1,4)-ß-glucanase isoenzyme EII under the control of a promoter of barley D-Hordein gene Hor3-1 was introduced into barley cultivar Golden Promise via Agrobacterium-mediated transformation, and transgenic plants were regenerated after hygromycin selection. The T2 generation of proHor3:HvGlb2 transgenic lines showed increased activity of (1,3;1,4)-ß-glucanase in grains. Total ß-glucan content was reduced by more than 95.73% in transgenic grains compared with the wild-type control. Meanwhile, over-expression of (1,3;1,4)-ß-glucanase led to an increase in 1000-grain weight, which might be due to elevated amounts of starch in the grain. CONCLUSION: Manipulating the expression of (1,3;1,4)-ß-glucanase EII can control the ß-glucan content in grain with no apparent harmful effects on grain quality of transgenic plants. © 2016 Society of Chemical Industry.