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Objective To investigate the clinical characteristics of the hepatolenticular degeneration in children, and to clarify the significance of gene diagnosis in children with hepatolenticular degeneration. Methods A total of 75 patients with hepatolenticular degeneration were enrolled in the Department of Pediatrics, Peking Union Medical College Hospital from 2011 to 2018. All of them carried out a generation of gene sequencing for ATPase Cu2+ transporting beta polypeptide (ATP7B) gene and multiplex ligation-dependent probe amplification (MLPA) analysis. Results Among the 75 pediatric patients, 55 patients were asymptomatic and had elevated aminotransferases as the incidental findings. All the pediatric patients had decreased ceruloplasmin. Seventy-two of pediatric patients had 24-hour urinary copper＞40 μg/d. There were 16 cases that had Kayser-Fleischer(K-F) rings. Sixteen six out of 75(21.33%)cases were diagnosed clinically and 15 cases were＞7 years old. All the remaining patients needed genetic diagnosis. Sixty-six patients had two mutations and 9 patients had only one mutation, 1 had no mutation. Forty eight different mutations were found to be localized in ATP7B gene. These mutations included 32 missense mutations, 6 splice mutations, 5 deletion mutations, 2 repeated mutations, 2 insert mutations and 1 nonsense mutations. The most frequently three mutations were c.2333G＞T,p.R778L,c.2621C＞T, p.A874V,c.2975C＞T, p.P992L,whose allele frequencies were 30.49%,14.89%,9.92%. Conclusions The research showed that in young aged patients, the nervous system symptoms are not obvious and the positive rate of laboratory tests are lower than adults so is a challenge to clinical diagnosis. So Genetic testing is of great significance for the early diagnosis and early treatment of disease in pediatric patients.

The Ehlers-Danlos syndrome(EDS)is a rare inherent connective tissue disorder. The prevalence of EDS in the population is estimated at one out of ten thousand to one out of a hundred thousand. The vascular EDS(vEDS) are rare among the subtypes but are the worst in prognosis. The article reports a case of vEDS admitted to the hospital. The patient was a young man complaining of a sudden onset of aphasia in right hemiparalysis and severe left abdominal pain for unknown reasons. The diagnosis was made after the genetic testing. The patient suffered from vEDS. Then, the multi-disciplinary team(MDT)made a treatment plan tailored to this young patient. The complexity in classification and delusive presentations of the EDS make the correct diagnosis very challenging. This article hopes to report this case and to share the experiences to the better understanding of this disease.

Simple Summary: The current study aimed to investigate the virulence and resistance genes associated with Klebsiella pneumoniae isolated from the farms of four animal species in selected areas of Xinjiang, China, encompassing cows, sheep, chickens, and pigs. The sensitivity to antibiotics was evaluated. Genetic diversity was assessed using wzi allele typing and multilocus sequence typing. The findings shed light on the antibiotic resistance patterns and genetic diversity among K. pneumoniae isolates originating from different animal sources, highlighting the potential for inter-species transmission of this bacterium. Klebsiella pneumoniae (K. pneumoniae) is recognized as a zoonotic pathogen with an increasing threat to livestock and poultry. However, research on K. pneumoniae of animal origin remains limited. To address the gap, a comprehensive investigation was carried out by collecting a total of 311 samples from the farms of four animal species (dairy cow, chicken, sheep, and pig) in selected areas of Xinjiang, China. Isolates were identified by khe gene amplification and 16S rRNA gene sequencing. Genotyping of K. pneumonia isolates was performed using wzi typing and multilocus sequence typing (MLST). PCR was employed to identify virulence and resistance genes. An antibiotic susceptibility test was conducted using the Kirby–Bauer method. The findings revealed an isolation of 62 K. pneumoniae strains, with an average isolation rate of 19.94%, with the highest proportion originating from cattle sources (33.33%). Over 85.00% of these isolates harbored six virulence genes (wabG, uge, fimH, markD, entB, and ureA); while more than 75.00% of isolates possessed four resistance genes (blaTEM, blaSHV, oqxA, and gyrA). All isolates exhibited complete resistance to ampicillin and demonstrated substantial resistance to sulfisoxazole, amoxicillin/clavulanic acid, and enrofloxacin, with an antibiotic resistance rate of more than 50%. Furthermore, 48.39% (30/62) of isolates were classified as multidrug-resistant (MDR) strains, with a significantly higher isolation rate observed in the swine farms (66.67%) compared to other farms. Genetic characterization revealed the classification of the 62 isolates into 30 distinct wzi allele types or 35 different sequence types (STs). Notably, we identified K. pneumoniae strains of dairy and swine origin belonging to the same ST42 and wzi33-KL64 types, as well as strains of dairy and chicken origin belonging to the same wzi31-KL31-K31 type. These findings emphasize the widespread occurrence of drug-resistant K. pneumoniae across diverse animal sources in Xinjiang, underscoring the high prevalence of multidrug resistance. Additionally, our results suggest the potential for animal-to-animal transmission of K. pneumoniae and there was a correlation between virulence genes and antibiotic resistance genes. Moreover, the current study provides valuable data on the prevalence, antibiotic resistance, and genetic diversity of K. pneumoniae originating from diverse animal sources in Xinjiang, China. [ABSTRACT FROM AUTHOR]

Exonic deletions and duplications within DMD are the main pathogenic variants in Duchenne and Becker muscular dystrophies (DMD/BMD). However, few studies have profiled the flanking sequences of breakpoints and the potential mechanism underlying the breakpoints in different fragile regions of DMD. In this study, 896 Chinese male probands afflicted with DMD/BMD were selected from unrelated families and analyzed using multiplex ligation‐dependent probe amplification of the DMD gene, in which we identified exon deletions in 784 subjects and duplications in 112 subjects. Deletions occurred most frequently in the genomic region encompassing exons 45–55, accounting for 73% of all deletion patterns. Furthermore, to unravel the potential mechanism that induced breaks, DMD gene capture and sequencing were performed to identify the breakpoints in 37 subjects with deletions encompassing exons 45–55 of DMD; we found that DMD instability did not arise from a single cause; instead, long‐sequence motifs, nonconsensus microhomologies, low‐copy repeats, and microindels were embedded around the breakpoints, which may predispose DMD to instability. In summary, this study highlights the heterogeneous characteristics of the flanking sequences around the breakpoints and helps us to understand the mechanism underlying DMD gene instability. [ABSTRACT FROM AUTHOR]

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Objective: Schimke immuno-osseous dysplasia (SIOD), is an autosomal recessive inherited disease caused by SMARCAL1 (MIM:20606622) mutations, while in about half of the patients no any mutation in SMARCAL1 could be found. This disease involves multiple systems and is characterized by short and dissymmetric stature with spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections, and hyperpigmented macules. This study aimed to analyze SMARCAL1 gene of 2 unrelated suspected SIOD children, to make definite diagnosis, and find more SMARCAL1 mutation types of Chinese SIOD., Method: Two suspected Chinese Han male SIOD children who visited our hospital from 2008 to 2014, aged 3 y 6 m and 7 y 8 m, both were short and had spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections. After informed consent, they and their parents's DNA were extracted from blood. PCRs for all 16 exons of SMARCAL1 were performed and PCR products were purified by 2% gel electrophoresis and sequenced directly. Pathogenicity of missense variations was confirmed by SIFT and sequencing SMARCAL1 of fifty normal controls., Result: (1) Four gene variations were found in the two children: Two reported missense mutations c.1129G>C, p.Glu377Gln and c.1933C>T, p. Arg645Cys. Two splicing mutations c.1334+1G>A and c.2142-1 G>A were detected. (2) c.1129G>C, p.Glu377Gln were reported as a disease-causing mutations before, but it was an single nucleotide polymorphism (SNP) which was found in 15 of 50 normal controls. (3) Two novel splicing mutations were found in this study: c.1334+1G>A and c.2142-1 G>A., Conclusion: (1) We detected 3 disease-causing mutations in 2 SIOD children by SMARCAL1 gene analysis, while 2 splicing mutations were novel mutations. (2) c.1129G>C, p.Glu377Gln was a SNP but not a disease-causing mutation at least in Chinese population.

Objective: Blau syndrome (BS), an autosomal dominant inherited autoinflammatory disease, is caused by NOD2 mutations. This study aimed to analyze NOD2 gene of suspected BS patients to make definite diagnosis, find NOD2 mutation types and clinical features of Chinese BS cases, and find some clinical indications to identify BS by comparing BS and non-BS cases., Method: Eighteen suspected BS children (7 boys and 11 girls, age of first visit was from 1 y 8 m to 9 y 6 m) who visited Peking Union Medical College Hospital from 2006 to 2014 and their parents's DNA were extracted from 4 ml blood specimens. PCR was performed for exon 4 of NOD2 and PCR products were purified by 2% gel electrophoresis and sequenced directly. Role of novel missense mutations in pathogenicity was analyzed by SIFT and sequencing NOD 2 of fifty normal controls. Clinical data of BS children diagnosed by NOD2 analysis were summarized and compared with the data of non-BS group., Result: (1) Twelve of eighteen suspected BS children were diagnosed as BS by NOD2 analysis, and the remaining 6 were excluded. Seven missense mutations were detected, 4 were reported before: c.1000C>T, p. Arg 334Trp; c.1001G>A, p. Arg334Gln; c.1538T>C, p. Met513Thr; c.1759C>T, p. Arg587Cys. Three novel mutations were found: c. 1147 G>C, p.Glu383Gln; c.1471A>T, p. Met491Leu; c.2006A>G, p.His669Arg. (2) Chronic symmetric arthritis and multi-joints periarticular hydatoncus, which were painless with fluctuation, were found in all 12 BS children with NOD2 mutations. Skin rash, chronic symmetric arthritis, and recurrent uveitis were identified in 7 patients. Three patients had no skin rash, while 1 had no uveitis, 1 only had symmetric arthritis and multi-joints periarticular hydatoncus. Four children inherited the disease from father. (3) Compared with other 6 non-BS children, BS children had such different clinical characteristic (P < 0.05): All the BS cases had multiple periarticular hydatoncus, which always had no persistent fever, most had no elevated CRP, while non-BS group always had no hydatoncus, most had persistent fever, all had elevated CRP., Conclusion: The 12 BS children were diagnosed by NOD2 analysis; 7 missense mutations were detected, 3 were novel mutations, adding new findings to human NOD2 mutations. Although classic BS was characterized by skin rash, arthritis, and eye involvement, some presented with less than 3 of the classic features. Chronic symmetric arthritis and multi-joints periarticular hydatoncus were the most comment fetures. Comparing with non-BS group, all BS cases had multi hydatoncus surrounding multi-joints, always had no persistent fever, most had no elevated CRP. Those features may distinguish BS in clinical settings.

Objective: To investigate the clinical and genetic features of 2 patients with Rubinstein-Taybi syndrome., Method: Using next generation sequencing (NGS) the CREBBP and EP300 genes of 2 children who were diagnosed as Rubinstein-Taybi syndrome at Peking Union Medical College Hospital. The mutations identified by NGS were verified by PCR were analyzed., Result: The 2 patients at the age of 5 months and 4.5 years manifested short stature (the height were 60 cm and 99 cm respectively), low hairline, thick and dense hair and eyebrows, long lash, epicanthus of both eyes, protruded supercilliary arch, broad and flat thumbs and halluces, and particular facial abnormalities. Patient 2 had language retardation besides. One missense mutation of c.3535A>G, p.Ser1179Gly was found in CREBBP gene in patient 1 and one microdeletion mutation of c.4995&#95;4999delCGCCT, p. Ala1666Pro fs66x was found inpatient 2. Both mutations were reported for the first time., Conclusion: Rubinstein-Taybi syndrome is characterized by mental and growth retardation, wide and flat thumbs and first toes, and dysmorphic facial features. CREBBP is one of the causative genes. Mutation detection on CREBBP gene can confirm the diagnosis of Rubinstein-Taybi syndrome.