[Screening for Duchenne muscular dystrophy in newborns in the Ningxia region]. / å®å¤åœ°åŒºæ–°ç”Ÿå„¿æœæ°è‚Œè¥å »ä¸è‰¯ç—‡ç­›æŸ¥.

OBJECTIVES: To evaluate the incidence rate of Duchenne muscular dystrophy (DMD) in the male newborns in the Ningxia region and establish a critical threshold for screening DMD in newborns to distinguish between the normal population and affected individuals. METHODS: A total of 10 000 male newborns were screened using immunofluorescence analysis of creatine kinase isoenzyme concentrations in heel spot dried blood specimens. Newborns with the concentrations higher than the critical threshold were recalled for serum creatine kinase measurements. Genetic testing was performed to confirm diagnosis in cases showing abnormalities. RESULTS: Among the screened 10 000 male newborns, two were confirmed to have DMD through genetic testing, resulting in a preliminary estimated incidence rate of 1/5 000 for male newborns in the Ningxia region. The critical threshold for creatine kinase isoenzyme concentration in newborns in this region was determined to be 468.57 ng/mL. CONCLUSIONS: Screening for DMD in newborns is feasible in the Ningxia region. Early screening, diagnosis, and treatment of DMD can improve the quality of life for affected individuals and help families make informed decisions regarding further pregnancies.

Identification of gene mutations in six Chinese patients with maple syrup urine disease.

Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD. Methods: Clinical examination was carried out for patients and used blood tandem mass spectrometry (MS/MS), urine gas chromatography-mass spectrometry (GC/MS), and the application of high-throughput sequencing technology for detection. Validate candidate mutations by polymerase chain reaction (PCR)-Sanger sequencing technology. Bioinformatics software analyzed the variants' pathogenicity. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of BCKDHA and BCKDHB proteins. Result: A total of six MSUD patients were diagnosed, including four males and two females. Nine variants were found in three genes of six MSUD families by high-throughput sequencing, including four missense mutations: c.659C>T(p.A220V), c.818C>T(p.T273I), c.1134C>G(p.D378E), and c.1006G>A(p.G336S); two non-sense mutations: c.1291C>T(p.R431*) and c.331C>T(p.R111*); three deletion mutations: c.550delT (p.S184Pfs*46), c.718delC (p.P240Lfs*14), and c.795delG (p.N266Tfs*64). Sanger sequencing's results were consistent with the high-throughput sequencing. The bioinformatics software revealed that the mutations were harmful, and the prediction results of Swiss PDB Viewer suggest that variation affects protein conformation. Conclusion: This study identified nine pathogenic variants in the BCKDHA, BCKDHB, and DBT genes in six MSUD families, including two novel pathogenic variants in the BCKDHB gene, which enriched the genetic mutational spectrum of the disease. High-throughput sequencing is essential for the MSUD's differential diagnosis, early treatment, and prenatal diagnosis.

A multicenter prospective study of next-generation sequencing-based newborn screening for monogenic genetic diseases in China.

BACKGROUND: Newborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies. METHODS: We designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS. With this panel, a large-scale, multicenter, prospective multidisease analysis was conducted on dried blood spot (DBS) profiles from 21,442 neonates nationwide. RESULTS: We presented the positive detection rate and carrier frequency of diseases and related variants in different regions; and 168 (0.78%) positive cases were detected. Glucose-6-Phosphate Dehydrogenase deficiency (G6PDD) and phenylketonuria (PKU) had higher prevalence rates, which were significantly different in different regions. The positive detection of G6PD variants was quite common in south China, whereas PAH variants were most commonly identified in north China. In addition, NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants, which were normal in conventional NBS, but were confirmed later as abnormal in repeated biochemical testing after recall. Eighty percent of high-frequency gene carriers and 60% of high-frequency variant carriers had obvious regional differences. On the premise that there was no significant difference in birth weight and gestational age, the biochemical indicators of SLC22A5 c.1400C > G and ACADSB c.1165A > G carriers were significantly different from those of non-carriers. CONCLUSIONS: We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods. Our data also showed that the prevalence of diseases has significant regional characteristics, which provides a theoretical basis for screening diseases in different regions.

Clinical significance of miR-139-5p and FGF2 in ovarian cancer.

PURPOSE: To estimate the expression and clinical significance of miR-139-5p and fibroblast growth factor 2 (FGF2) in ovarian cancer (OC). METHODS: Of the 198 female patients undergoing surgical treatment in our hospital, 101 patients with ovarian tumor resection were allocated in a study group and 97 with ovarian resection for benign lesions were allocated in a control group. MiR-139-5p and FGF2 expression was quantified, and associations between miR-139-5p and FGF2 and clinicopathological features of OC were analyzed, as well as their diagnostic performances (receiver operating characteristic (ROC) curve). RESULTS: The study group presented lower miR-139-5p level and higher FGF2 level (both p<0.05). Significant associations of miR-139-5p and FGF2 with tumor differentiation and clinical stage were noted in OC (p<0.05). MiR-139-5p was reversely associated with clinical stage and positively associated with tumor differentiation (p<0.05), FGF2 was positively correlated with clinical stage and negatively correlated with tumor differentiation (p<0.05). The overall survival in the study group was 70.41%. The survival in high miR-139-5p expression group and low FGF2 expression group improved remarkably (p<0.05). The area under the curve (AUC) of combined detection (0.91) was higher than that of single detection. CONCLUSION: MiR-139-5p shows a decreased expression and FGF-2 shows an increased expression in OC, and they are associated with clinical stage and tumor differentiation. Combined detection of miR-139-5p and FGF-2 contributes to the diagnosis and treatment of OC, and is an available biomarker for the diagnosis and prognosis of patients.

Ethnic preference distribution of inborn errors of metabolism: A 4-year study in a multi-ethnic region of China.

Chinese newborns have been screened for inborn errors of metabolism (IEM) for over 20 years. Although China features 56 different ethnic groups, there are no specific data describing the incidence of such genetic errors across difference ethnicities. To understand the ethnic preference distribution of the incidence and variants of IEM in the Ningxia Hui Autonomous Region of China, 189,354 newborns from 2016 to 2019 were screened by tandem mass spectrometry, including 87,482 from the Han ethnic population, 88,229 from the Hui population, 1,103 from other ethnicities, and 12,540 infants without ethnic registration. Suspected cases then underwent specific genetic profiling by targeted next generation sequencing. In total, 160 patients were diagnosed with 17 types of IEM, with a significant higher incidence in Hui infants (1/1,003) than in Han infants (1/1,232). Five diseases (eight patients) were specifically detected in Han infants, while three were exclusively diagnosed in six Hui infants. For shared diseases, the variants of keys genes also showed ethnic preference. Our findings enhance our understanding of the genetics underlying IEM, thus promoting the development of treatment plans for patients from different areas or ethnicities in China.

[Screening and follow-up treatment of 160 046 neonates with congenital adrenal hyperplasia in Ningxia, China].

OBJECTIVE: To investigate the incidence of congenital adrenal hyperplasia (CAH) and treatment outcomes in neonates in Ningxia, China. METHODS: The clinical data of CAH screening for 160 046 neonates who were born in midwifery institutions in Ningxia from July 2014 to March 2016 were analyzed. RESULTS: Among the 160 046 neonates who underwent CAH screening, 70 (0.044%) obtained a positive result and 11 were diagnosed with CAH; the incidence rate of CAH was 1/14 550 (0.069‰). Among the 11 neonates diagnosed with CAH, 9 had the salt wasting type (2 died) and 2 had simple virilization. The 9 neonates were given glucocorticoids immediately once diagnosed and all of them achieved good growth and development. CONCLUSIONS: The incidence of neonatal CAH in Ningxia is 1/14 550. It is very necessary to carry out CAH screening in Ningxia, and active treatment can improve the prognosis of neonates with CAH.

[Analysis of mutations in exon 7 of phenylalanine hydroxylase gene among children with phenylketonuria in Ningxia, China].

OBJECTIVE: To investigate the type and frequency of mutations in exon 7 of phenylalanine hydroxylase (PAH) gene among children with phenylketonuria (PKU) in Ningxia, China and to provide a basis for the genetic diagnosis and prenatal diagnosis of PKU in this region. METHODS: Direct sequencing of PCR product was performed to analyze the sequences of exon 7 and its flanking introns of 146 PAH alleles in 73 children with typical PKU (39 cases of Hui nationality and 34 cases of Han nationality) in Ningxia. RESULTS: Six mutations were detected, including R243Q (14.4%), R241C (6.8%), IVS7+2T→A (2.7%), L255S (0.7%), G247V (0.7%), and G247R (0.7%). The overall frequency of mutations (missense mutation and splice site mutation) in exon 7 was 26.0% (38/146). The detection rate of R241C mutation was significantly higher in children of Hui nationality than in children of Han nationality(10% vs 3%; P<0.05). CONCLUSIONS: In Ningxia, R243Q mutation in exon 7 of PAH gene is most common in children with PKU, followed by R241C. The frequency of R241C mutation in exon 7 of PAH gene varies between children with PKU of Hui and Han nationality.

[Analysis for phenylalanine hydroxylase gene mutations in 35 ethnic Hui children from Ningxia with phenylketonuria].

OBJECTIVE: To determine the type and frequency of phenylalanine hydroxylase gene (PAH) mutations in ethnic Hui patients from Ningxia with phenylketonuria (PKU). METHODS: For 35 PKU children patients and 50 healthy individuals, all exons and promoters of the PAH gene were analyzed with PCR and direct sequencing. RESULTS: Twenty mutations, including 8 missense mutations (40%), 5 nonsense mutations (25%), 4 splice site mutations (20%) and 3 deletion mutants (15%) were discovered. The overall detection rate was 68.57% (48/70). Common mutations have included R243Q (12.86%), R241C (11.43%), EX6-96A to G (5.71%), Y356X (5.71%), R413P(4.29%) and Q232X(4.29%), whilst rarer ones have included S16fsX10 (2.86%), R111X (2.86%) and L430P (2.86%). Among these, S16fsX10, L430P, D222G and IVS11+ 1G to A have not been reported previously. Y414X and S303fsX38 have not been reported in Hui ethnic group. No mutation was detected in the 50 normal controls. CONCLUSION: The types and distribution of PAH gene mutations in ethnic Hui from Ningxia have been different from other areas of China. The mutations also showed a rich diversity.

[Growth status of children under 7 years in Wuzhong City, Ningxia Hui Autonomous Region, China and its influential factors].

OBJECTIVE: To investigate the growth status of children under 7 years in Wuzhong City, Ningxia Hui Autonomous Region, China and its influential factors, and to provide a basis for related intervention measures. METHODS: Children under 7 years were selected from two county-level districts in Wuzhong by stratified cluster sampling, and their growth status were evaluated by the Z score method. RESULTS: The prevalence rates of growth retardation, underweight, and wasting were 12.58%, 5.71%, and 5.55% respectively. The height-for-age Z score, weight-for-age Z score, and weight-for-height Z scores were -0.26±2.50, 0.29±4.54. and 0.65±3.02 respectively. There were significant differences in the prevalence rate of wasting among children of different ethnic groups (P<0.05); also, there were significant differences in the prevalence rates of growth retardation and underweight among children from different regions and with different age (P<0.05). The main influential factors for growth retardation were region (OR=0.369, P<0.001), ethnic groups (OR=1.694, P=0.027), and age (OR=1.143, P=0.002). The main influential factors for underweight were region (OR=0.453, P=0.001) and age (OR=1.204，P=0.002). The main influential factor for wasting was nation (OR=1.735, P=0.024). CONCLUSIONS: In Wuzhong, children under 7 years have poor growth status, which are related to ethnic groups, region, and age.