Objective To investigate the frequency and distribution characteristics of gene mutations in children with phenylalanine hydroxylase(PAH)deficiency in Xinjiang.Methods A total of 230 children diag-nosed with PAH deficiency in Urumqi Maternal and Child Health Care Hospital from January 1st,2015 to February 28th,2023 were enrolled in the study.The variation of PAH gene was analyzed and the variation sites of PAH gene in children with different phenotypes were compared.Results A total of 441 PAH gene va-riants were detected in 230 children with PAH deficiency in Xinjiang,with a total detection rate of 95.87％.A-mong them,2 variants were detected in 227 cases,only 1 variant was detected in 2 cases,and 3 variants were detected in 1 case.217 cases were complex heterozygous variants,and 10 cases were homozygous variants.The high-frequency variant loci were c.158G＞A[23.39％(102/441)],c.728G＞A[11.70％(51/441)],c.688G＞A[5.05％(22/441)],c.721C＞T[3.90％(17/441)],c.611A＞G[3.67％(16/441)],c.1238G＞C[3.21％(14/441)].The high-frequency variant loci for classic PKU were c.728G＞A,c.331C＞T,and c.782G＞A;the high-frequency variant loci for mild PKU were c.721C＞T,c.1068C＞A,and c.1301C＞A;the high-frequency variant loci for children with mild HPA were c.158G＞A and c.688G＞A.There were significant differences in the frequency of high frequency mutations among the above three phenotypes(P＜0.05).Conclusion Mild HPA predominates in children with PAH deficiency in Xinjiang.The hotspot loci of the PAH gene in Xinjiang have been clarified,and specific PAH gene loci have been observed in the three different phenotypes,which can provide theoretical basis for prenatal diagnosis and clinical genetic counselling.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

【Objective】 To investigate the influencing factors behind the follow-up compliance of patients with low/no phenylketonuria (PKU) for special medical use, in order to provide a basis for regulating the follow-up of PKU patients and ensuring the effectiveness of special diet treatment. 【Methods】 A survey was conducted on PKU patients treated in Urumqi Maternal and Child Health Hospital for over 1 year, from January 2010 to December 2020. Interviews and questionnaires were conducted with their caregivers to collect and analyze the current status of PKU patients undergoing special diet treatment, and to identify the influencing factors behind their compliance with follow-up treatment. 【Results】 Patients who had received neonatal disease screening, neonatal gene diagnosis, and maternal Down′s screening during pregnancy had better compliance, with statistically significant differences (χ²=5.753, 10.993, 9.189, P<0.05). PKU children with parents who had a college education or above showed significantly higher adherence to special diet treatment (χ²=8.321, 7.415, P<0.05). PKU children with parents having a fixed occupation also showed higher compliance, with a statistically significant difference (χ²=20.626, 7.895, P<0.05). Patient age, interval of buying special diet, number of blood samples sent and enrollment of normal age, all had a significant impact on the follow-up compliance of PKU patients with special diet (χ²=19.443, 8.090, 69.482, 12.001, P<0.05). 【Conclusions】 PKU is a treatable genetic metabolic disease. Strengthening health education, formulating standardized follow-up plans and procedures, and improving follow-up treatment compliance are crucial in enhancing the treatment and follow-up effectiveness of PKU patients.

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.

Objective To carry out carrier screening for spinal muscular atrophy(SMA)in 3 302 preg-nant women from Xinjiang region and preliminarily determine the SMA carrier frequency among pregnant women in the region.Methods A total of 29 089 pregnant women who underwent prenatal visits at this hos-pital from April 2020 to February 2023 were educated,of whom 3 302 were received SMA carrier screening.SMA carriers were screened by detecting the copy numbers of SMN1 exons 7(E7)and 8(E8)using quantita-tive fluorescence PCR.Multiplex ligation-dependent probe amplification(MLPA)was used for prenatal diag-nosis of high-risk fetuses in couples who were both SMA carriers.Results The acceptance rate of SMA carri-ers screening was 11.35％.Among the 3 302 pregnant women,58 were found to be SMA carriers,and the total carrier frequency was 1.76％(1/57).Among them,there were 45 cases of Han ethnicity,with a carrying fre-quency of 1.63％(1/61),and there were 13 cases of ethnic minorities,with a carrying frequency of 2.39％(1/42).Among the 58 carriers,46 spouses were received SMA screening,and the results showed that two couples were both SMA carriers.Further prenatal diagnosis was performed,and the results of MLPA indicated that the fetuses were all heterozygous deletions of SMN1 E7 and E8,suggesting continued pregnancy.Conclusion This study has preliminarily determined the SMA carrier frequency among pregnant women in Xinjiang region.SMA carrier screening in pregnant women and prenatal diagnosis of high-risk fetuses are of great significance for the prevention and control of birth defects.

Objective:To study the genetic profiles of phenylalanine hydroxylase (PAH) gene mutations in neonates with phenylketonuria (PKU) in Xinjiang.Methods:From January 2015 to December 2021,neonates born and genetically diagnosed with PKU in our region were retrospectively included. The genetic profiles of different ethnic groups were analyzed and compared with PKU patients from central, northwest and northern regions of China.Results:A total of 131 neonates with PKU were enrolled, including 82 Han, 25 Hui and 20 Uyghur patients, 4 cases of other ethnic groups. 46, 20 and 14 types of pathogenic variants were detected in each ethnic group with detection rates of 95.1% (156/164), 66.0% (33/50), and 60.0% (24/40), respectively. The variants were mainly missense mutations and located in exons 2, 3, 6,7 and 11. The most common loci in Hui patients were c.158G>A (18.2%), c.728G>A (18.2%) and c.898G>T (9.1%). The most common loci in Uyghur patients were c.158G>A (33.3%), c.355C>T (12.5%) and c.1068C>A (8.3%). c. 898G>T might be most unique in Hui patients and c.355C>T most unique in Uyghur patients in Xinjiang. A novel variant of PAH gene, c.828G>C (p.M276I) in exon 7 was identified. Compared with northern, central and northwestern regions of China, PKU patients in Xinjiang had significantly higher incidence of c.158G>A mutation and lower incidence of c.728G>A mutation ( P<0.05). Conclusions:Missense mutations of PAH gene are common in some regions of Xinjiang. The compositions of PAH gene variations are similar to northwest and northern China with significant differences in hotspots of mutations.

OBJECTIVE: To summarize the genetic diagnosis, low-depth copy number variation sequencing (CNV-seq) and prenatal finding in 7 fetuses with 2p16.3 deletions only involving the NRXN1 gene. METHODS: The 7 fetuses have all been found to have loss of heterozygosity at 2p16.3 by CNV-seq, which were verified by quantitative real-time PCR (qPCR). Specific regions of NRXN1 gene deletions were identified, and the CNVs were verified in their parents. Outcome of the pregnancies were followed up. RESULTS: Among 16 502 prenatal samples, 7 fetuses were found to harbor a 120 kb ~ 900 kb microdeletion in the 2p16.3 region, which yielded a prevalence of 0.424‰. The deleted region mainly involved 50 200 000-51 880 000 positions of chromosome 2 and involved only the NRXN1 gene. All of the 7 fetal CNVs were confirmed by qPCR, including 2 cases with heterozygous deletion of exons 1 to 6, 1 with heterozygous deletion of exons 1 to 19, 1 with heterozygous deletion of exons 19 to 22, and 3 with heterozygous deletion of introns 6 to 7 of the NRXN1 gene. Verification in the parents had found that one deletion was inherited from the father, 1 was from the mother, 2 cases were de novo in origin, whilst the remaining 3 had refused parental verification. After genetic counseling, one couple had elected induced abortion, 1 case has not been born yet, whilst the other 5 cases were born healthy. Follow up had identified no mental abnormalities among the children. CONCLUSION Seven fetuses with heterozygous 2p16.3 deletions only involving the NRXN1 gene were detected by CNV-seq. The specific deletion of the NRXN1 gene was verified by qPCR. Prenatal genetic counseling and fertility guidance has been provided to the particular family by combining the results of CNV testing, pedigree analysis and pregnancy outcome.
Female ; Humans ; Pregnancy ; Calcium-Binding Proteins/genetics* ; Cell Adhesion Molecules, Neuronal/genetics* ; DNA Copy Number Variations ; Nerve Tissue Proteins/genetics* ; Neural Cell Adhesion Molecules/genetics* ; Prenatal Diagnosis ; Real-Time Polymerase Chain Reaction ; Infant, Newborn

Objective:To explore the characteristics of patients with Alagille syndrome(ALGS), so as to provide evidence for early clinical diagnosis.Methods:The clinical data of 13 children diagnosed with ALGS in Children′s Hospital of Chongqing Medical University from February 2014 to November 2018 was retrospectively analyzed, and some children were followed up.Results:Among the 13 patients, 12 cases(92.3%) had cholestasis, 8 cases(61.5%) with heart malformation, 5 cases(38.5%) with characteristic facial features, 5 cases(38.5%) with pruritus, and 1 case(7.7%) with a positive family history.Among the 7 pediatric ophthalmologists, 2 patients suffered from ocular lesions.Seven patients underwent spine radiography, and 1 patient had typical butterfly vertebra.In the 9 cases with hepatic pathology, 4 cases had partial hepatic sinus pressure or occlusion, 1 case had no small bile duct in part of the portal area, 4 cases had small bile duct hyperplasia, and 5 cases underwent biliary tract exploration.Genetic testing of 12 children with ALGS showed JAG1 gene mutation in 8 cases and NOTCH2 gene mutation in 4 cases.Among the 11 followed up patients, 8 cases were in stable condition, 1 patient with progressive cirrhosis was registered for liver transplantation, 1 patient died of liver failure, and 1 patient developed with drug-induced liver injury at the age of 4 months had progressive liver failure, and the jaundice was gradually subsided after liver transplantation. Conclusions:ALGS may appear on multiple systems involvement, and it demonstrates variable clinical expressivities and incomplete penetrance, thus bring certain difficulties to clinical diagnoses.It′s easily misdiagnosed as biliary atresia in infancy.Genetic testing is integral in the diagnosis of ALGS.