Objective To investigate gene mutations in a pedigree with oculocutaneous albinism by using targeted next-generation sequencing technology.Methods Clinical data were collected from a pedigree with oculocutaneous albinism.Genomic DNA was extracted from peripheral blood cells of the proband and his parents.High-throughput sequencing technology was used for sequence analysis of coding regions in exons of 29 genes including TYR,OCA2,TYRP1 and SLC45A2 in the proband to find potential pathogenic gene mutations.Sanger sequencing was conducted to detect the corresponding genetic loci in the parents.Results Two heterozygous mutations were identified in the TYR gene of the proband,including a novel mutation c.534G ＞ C (p.Trp178Cys) and a known mutation c.1147G ＞ A (p.Asp383Asn).The detection of the TYR gene mutations in the parents of the proband showed that the c.534G ＞ C and c.1147G ＞ A mutations in the proband were inherited from his father and mother respectively.Conclusion A novel pathogenic mutation c.534G ＞ C in the TYR gene is identified in the pedigree with oculocutaneous albinism by using targeted next-generation sequencing technology.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with split hand/foot malformation (SHFM). METHODS: Genomic DNA of the proband and other affected members was extracted from peripheral blood samples. Chromosomal microarray analysis was employed to detect genome-wide copy number variations (CNVs). RESULTS: A 400 kb microduplication was identified in the 10q24.31-q24.32 region among all affected individuals. The microduplication has involved four genes, namely LBX1, BTRC, POLL and DPCD, in addition with part of FBXW4 gene. CONCLUSION The 10q24.31-q24.32 microduplication has segregated with the disease phenotype in this pedigree and probably underlay the SHFM malformation in the patients.
Asian Continental Ancestry Group ; Chromosome Duplication ; Chromosomes, Human, Pair 10 ; genetics ; DNA Copy Number Variations ; Foot Deformities, Congenital ; genetics ; Genetic Testing ; Hand Deformities, Congenital ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Pedigree

Objective:To summarize the surgical treatment strategy for aortic injury caused by trauma.Methods:From January 2009 to January 2018, 34 patients with TAI were treated in Beijing Anzhen Hospital. 10 had hypertension. 23 cases were males. There were 31 cases caused by traffic accidents, 2 cases were fall injuries, and 1 case was bruise. 9 cases were thoracic aortic pseudoaneurysm, 6 cases were thoracic aorta, and 19 cases were aortic dissection. 29 patients underwent TEVAR and 5 patients underwent OR (2 patients with type A aortic dissection undergoing Bentall + Sun's procedure, 1 patient with type B aortic dissection and 2 patients with thoracic aortic pseudoaneurysm undergoing stented elephant trunk procedure).Results:The follow-up time was (45.09±23.10) months. The mean age of patients undergoing OR or TEVAR was (44.80±20.57) years old, (45.93±11.01) years old; the mean operation time was(403.20±30.30) minutes, (105.72±27.76) minutes; the mean hospitalization (19.00±6.04), (5.76±3.08) days. There were no deaths in the two groups. 2 patients uundergoing TEVAR had left upper limb numbness.Conclusion:The treatment of patients with TAI should be based on the general condition, the classification of injury, the involving regions and anatomical features to choose different treatments. In addition, the long-term prognosis of patients remains to be determined.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with autosomal dominant late-onset non-syndromic hearing loss (NSHL). METHODS: Clinical data of the pedigree were collected. Genomic DNA was extracted from peripheral blood samples of the proband and other family members. Trio whole exome sequencing was carried out for 19 396 genes to identify potential pathogenic variants. Sanger sequencing was carried out to verify the candidate variant in the pedigree. RESULTS: The proband and his father were found to carry a c.1183+1delG p.? variant of the DFNA5 gene. The variant was confirmed to be co-segregating with the disease phenotype in the pedigree. CONCLUSION The c.1183+1delG p.? variant of the DFNA5 gene probably underlay the late onset NSHL in this pedigree. Above finding has enabled accurate genetic counseling for this pedigree.
Age of Onset ; China ; Hearing Loss, Sensorineural/genetics* ; Humans ; Male ; Mutation ; Pedigree ; Receptors, Estrogen/genetics*

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for a Chinese pedigree with Lesch-Nyhan syndrome (LNS) but no specimen from the affected probands. METHODS: All affected individuals in this pedigrees were male and had deceased during childhood, with no biological specimen left. Based on their typical neurological dysfunction and tendency for self-mutilation, the diagnosis of LNS was suspected. Sanger sequencing was carried out to detect potential variant of the HPRT1 gene among female members from the pedigree. Following the identification of the pathogenic variant, prenatal diagnosis was provided for a high-risk fetus. RESULTS: The proband's mother and three other females were found to harbor heterozygous c.500_501delGGinsC (p.Arg167fs*23) variant of the HPRT1 gene, which was unreported previously. Prenatal diagnosis showed that the fetus was a male and had inherited the same pathogenic variant. CONCLUSION The c.500_501delGGinsC variant of the HPRT1 gene probably underlay the LNS in this pedigree. Above finding has provided a basis for prenatal diagnosis and genetic counseling for this pedigree.
Male ; Female ; Humans ; Pregnancy ; Lesch-Nyhan Syndrome/genetics* ; Pedigree ; Hypoxanthine Phosphoribosyltransferase/genetics* ; Prenatal Diagnosis ; China ; Mutation

Objective To investigate the incidence of neonatal hyperphenylalaninemia(HPA)and analyze the characteristics of HPA gene mutations in the Yangzhou area.Methods From Janu-ary 2013 to December 2022,285,549 newborns in Yangzhou were screened for HPA using either the ninhydrin fluorescence method or tandem mass spectrometry.Urinary pterin analysis,erythrocyte di-hydrobiopterin reductase activity measurement and genetic diagnosis were performed to screen positive individuals.Results A total of 29 cases were confirmed as HPA,including 3 cases of tetrahydro-biopterin(BH4)deficiency and 26 cases of phenylalanine hydroxylase(PAH)deficiency.The over-all incidence of HPA in Yangzhou was 1/9,847,with the incidence of PAH deficiency being 1/10,983,which were slightly higher than the national average but lower than other regions in Jiangsu Prov-ince.Among the cases,13(44.83％)were classic phenylketonuria(PKU),7(24.14％)were mild PKU,and 6(20.69％)were mild HPA.Sixteen patients with PAH gene mutations were all com-pound heterozygotes,with one case exhibiting three-site mutations.PAH gene mutations were predomi-nantly missense mutations,primarily concentrated in exon 7,followed by exon 6,with E7 c.728G＞A(21.21％)being the most frequent mutation.Three cases of BH4 deficiency were detected with PTS gene mutations,including 1 homozygous mutation and 2 compound heterozygous mutations.E5 c.259C＞T was the high-frequency PTS mutation gene in Yangzhou.Conclusion HPA has a certain incidence in Yangzhou,with classic PKU being the predominant type.This study clarified the characteristics of PAH and PTS gene mutations in Yangzhou,enriching the HPA gene database.

Objective To investigate the incidence of neonatal hyperphenylalaninemia(HPA)and analyze the characteristics of HPA gene mutations in the Yangzhou area.Methods From Janu-ary 2013 to December 2022,285,549 newborns in Yangzhou were screened for HPA using either the ninhydrin fluorescence method or tandem mass spectrometry.Urinary pterin analysis,erythrocyte di-hydrobiopterin reductase activity measurement and genetic diagnosis were performed to screen positive individuals.Results A total of 29 cases were confirmed as HPA,including 3 cases of tetrahydro-biopterin(BH4)deficiency and 26 cases of phenylalanine hydroxylase(PAH)deficiency.The over-all incidence of HPA in Yangzhou was 1/9,847,with the incidence of PAH deficiency being 1/10,983,which were slightly higher than the national average but lower than other regions in Jiangsu Prov-ince.Among the cases,13(44.83％)were classic phenylketonuria(PKU),7(24.14％)were mild PKU,and 6(20.69％)were mild HPA.Sixteen patients with PAH gene mutations were all com-pound heterozygotes,with one case exhibiting three-site mutations.PAH gene mutations were predomi-nantly missense mutations,primarily concentrated in exon 7,followed by exon 6,with E7 c.728G＞A(21.21％)being the most frequent mutation.Three cases of BH4 deficiency were detected with PTS gene mutations,including 1 homozygous mutation and 2 compound heterozygous mutations.E5 c.259C＞T was the high-frequency PTS mutation gene in Yangzhou.Conclusion HPA has a certain incidence in Yangzhou,with classic PKU being the predominant type.This study clarified the characteristics of PAH and PTS gene mutations in Yangzhou,enriching the HPA gene database.

Objective To explore the value of chromosomal microarray analysis(CMA)for the diagnosis of early spontaneous abortion,and to investigate the relationship between chromosomal abnormalities and early spontaneous abortion.Methods A total of 432 cases embryos were collected from June 2017 to December 2022 which occur early spontaneous abortion in Yangzhou Maternal and Child Health Hospital.We retrospectively analyze the results of chromosomal microarray analysis,and analyze the correlation between different gestational weeks and numerical chromosomal abnormalities and copy number variations.Results A total of 428 specimens were successfully analyzed by the CMA.Chromosomal abnormalities were identified in 270 specimens,including 212 cases of numerical chromosomal abnormalities,53 cases of copy number variations,and 5 cases of uniparental disomy.Most chromosomal abnormalities are trisomies,with 16-trisomy was the most common.Among the copy number variations,31 cases of pathogenic and likely pathogenic were detected,and 22 cases of clinically unknown copy number abnormalities were detected.There was no statistically significant difference in numerical chromosomal abnormalities among different gestational weeks(P>0.05),while the positive rate of copy number variations was highest at 10-11+6 weeks of pregnancy.Conclusion CMA can clarify the etiological diagnosis of early spontaneous abortion.It can not only detect chromosomal abnormalities,but also can detect copy number variations and even chromosome microdeletion syndrome,chromosome microduplication syndrome.In the study,numerical chromosomal abnormalities are the main cause of spontaneous abortion.

Objective:To retrospectively analyze the gender differences in the clinical characteristics and perioperative outcomes of patients with type A aortic dissection in our institution.Methods:From January 2019 to January 2020, total 405 patients underwent surgical treatment for type A aortic dissection at Beijing Anzhen Hospital, including extensive aortic repair (total aortic arch replacement combined with stenting elephant trunk implantation) and limited aortic repair. In the entire cohort, male 295 cases, female 110 cases. All measures in this study were expressed as ± s or median(quartiles) and analyzed by Student t test for variables or non- parametric tests; count data were expressed as frequencies and percentages and analyzed by χ2 test and Fisher exact probability test. Independent risk factors were analyzed by logistic multivariate regression. Results:Females were older than males[(53.3 ± 12.4)years old vs. (47.1 ± 11.0)years old, P<0.001] and had significantly higher proportion of diabetes(9.1% vs. 4.1%, P=0.047) and previous cerebrovascular disease (11.8% vs. 5.8%, P=0.038). Females had a lower proportion of total aortic arch replacement combined with elephant trunk implantation (64.5% vs. 82.7%, P<0.001), while aortic cross-clamp time[168.0(144.8, 201.5) minutes vs. 190.0 (163.0, 217.0) minutes, P<0.001] and CPB time[99.0 (79.8, 118.0) min vs. 107.0 (91.0, 126.0) min, P=0.006] were significantly shorter than males. Females had significantly higher rates of pulmonary infection (14.5% vs. 5.8%, P=0.004) and stroke than males (15.5% vs. 8.1%, P=0.030). The difference in the proportion of postoperative deaths between female and male TAAD patients was not statistically significant (3.6% vs. 7.8%). Logistics multivariable regression analysis found that female was an independent risk factor for postoperative stroke ( OR=2.574, 95% CI: 1.198-5.531, P=0.015) and pulmonary infection ( OR=2.610, 95% CI: 1.180-5.772, P=0.018). Conclusion:Gender did not affect mortality after TAAD repair significantly, but females increased the risk of stroke and pulmonary infection after TAAD surgery.

Objective:To analyze the long-term outcomes of hybrid arch repair(HAR) treating aortic arch pathologies.Methods:Between January 2009 and January 2018, 87 consecutive patients underwent HAR for aortic arch pathologies at Beijing Anzhen Hospital. 76 were males. 2 cases were in zone 0, 46 cases were in zone 1, and 39 cases were in zone 2. The zones of the aortic arch were defined following the Ishimaru classification.Results:Five(5.7%) operative death occurred. 13 patients(19.1%) died during the follow-up. The overall survival rate was 88.4%, 83.3%, 83.3%, 49.8% at 1, 3, 5, 10 year, respectively. Multivariate Cox proportional risk analysis showed that stroke( HR=20.626, 95% CI: 2.698-157.685, P=0.004) was an independent risk factor for short-term death. Stroke( HR=16.234, 95% CI: 4.103-64.229, P<0.001) and spinal cord infury( HR=11.060, 95% CI: 2.150-56.893, P=0.004) were independent risk factors for long-term death. Conclusion:In conclusion, HAR could be an alternative procedure for the patients that are not suitable for open repair under the premise of strict control of indications. In the future, the risk assessment system and uniform operational indications for HAR should be further established.