Asian Continental Ancestry Group ; Cardiomyopathy, Hypertrophic ; genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; LIM Domain Proteins ; genetics ; Male ; Muscle Hypertonia ; genetics ; Muscle Proteins ; genetics ; Mutation ; Young Adult

BACKGROUNDH syndrome (OMIM 612391) is a recently described autosomal recessive genodermatosis characterized by indurated hyperpigmented and hypertrichotic skin, as well as other systemic manifestations. Most of the cases occurred in the Middle East areas or nearby countries such as Spain or India. The syndrome is caused by mutations in solute carrier family 29, member 3 (SLC29A3), the gene encoding equilibrative nucleoside transporter 3. The aim of this study was to identify pathogenic SLC29A3 mutations in a Chinese patient clinically diagnosed with H syndrome.

METHODSPeripheral blood samples were collected from the patient and his parents. Genomic DNA was isolated by the standard method. All six SLC29A3 exons and their flanking intronic sequences were polymerase chain reaction (PCR)-amplified and the PCR products were subjected to direct sequencing.

RESULTSThe patient, an 18-year-old man born to a nonconsanguineous Chinese couple, had more extensive cutaneous lesions, involving both buttocks and knee. In his genomic DNA, we identified a novel homozygous insertion-deletion, c. 1269_1270delinsA, in SLC29A3. Both of his parents were carriers of the mutation.

CONCLUSIONSWe have identified a pathogenic mutation in a Chinese patient with H syndrome.

Abnormalities, Multiple ; diagnosis ; genetics ; Adolescent ; Asian Continental Ancestry Group ; Genetic Predisposition to Disease ; Humans ; Male ; Mutation ; Nucleoside Transport Proteins ; genetics ; Skin Abnormalities ; diagnosis ; genetics

We represented a 22-year-old male patient who developed rhabdomyolysis,acute kidney failure and acute hepatic failure and was finally diagnosed as multiple acyl-CoA dehydrogenase deficiency.The patient appeared temporary stable status after high dose vitamine-B2 supplement whereas deterioration was still fatal with pulmonary infection,acute respiratory failure and acute heart failure.

Objective:To evaluate the role of de novo mutations (DNMs) in Chinese patients with non-syndromic congenital microtia by using whole exome sequencing in patient-parent trios and to detect the pathogenic DNMs, if there are any. Methods:Twenty-four Chinese trio families with congenital microtia were recruited from March 2017 to July 2018 at the Plastic Surgery Hospital of Chinese Academy of Medical Sciences. The patients, aged from 6 to 10 years old, 15 males and 9 females, had unilateral microtia, including 15 on the left and 9 on the right. After informed consent, peripheral blood was collected from patients and their unaffected parents.Whole exome sequencing was performed on all patients and their parents. DNMs in the coding region and canonical splicing sites were detected, and the number of DNMs in each patient was obtained. Each DNM was classified according to the ACMG standards and guidelines for the interpretation of sequence variants. In-silico prediction was performed using different algorithms and databases considering both variant-and gene-level implications. ExAc database, VarCards, Human Splicing Finder 3.1 software were used to predict each variant’s pathogenicity, including loss of function variant, missense variant and nonsynonymous variant. Mouse genome information database was used to detect the expression of the homologous gene, and David 6.8 bioinformatics database was used for pathway enrichment analysis of candidate genes. The Online Mendelian Inheritance in Man database was used to query the correspondence between candidate genes and human diseases.Results:Twenty-three DNMs were detected in 24 microtia trios. In each patient, there was 0-3 DNMs with no significant difference in population. Twelve missense variants, eight synonymous variants, one nonsense, one start codon variant, and one inframe indel were detected. Among them, a nonsense LRP12 mutation was classified as pathogenic according to ACMG guidelines. However, none of the variants were considered disease-causing according to in-silico predictions.Conclusions:Increased number or mutational burden of DMNs are not observed in Chinese patients with microtia. DMNs is not the primary cause of microtia, although rare DNMs in responsible genes could occasionally lead to cases.

Objective:To evaluate the role of de novo mutations (DNMs) in Chinese patients with non-syndromic congenital microtia by using whole exome sequencing in patient-parent trios and to detect the pathogenic DNMs, if there are any. Methods:Twenty-four Chinese trio families with congenital microtia were recruited from March 2017 to July 2018 at the Plastic Surgery Hospital of Chinese Academy of Medical Sciences. The patients, aged from 6 to 10 years old, 15 males and 9 females, had unilateral microtia, including 15 on the left and 9 on the right. After informed consent, peripheral blood was collected from patients and their unaffected parents.Whole exome sequencing was performed on all patients and their parents. DNMs in the coding region and canonical splicing sites were detected, and the number of DNMs in each patient was obtained. Each DNM was classified according to the ACMG standards and guidelines for the interpretation of sequence variants. In-silico prediction was performed using different algorithms and databases considering both variant-and gene-level implications. ExAc database, VarCards, Human Splicing Finder 3.1 software were used to predict each variant’s pathogenicity, including loss of function variant, missense variant and nonsynonymous variant. Mouse genome information database was used to detect the expression of the homologous gene, and David 6.8 bioinformatics database was used for pathway enrichment analysis of candidate genes. The Online Mendelian Inheritance in Man database was used to query the correspondence between candidate genes and human diseases.Results:Twenty-three DNMs were detected in 24 microtia trios. In each patient, there was 0-3 DNMs with no significant difference in population. Twelve missense variants, eight synonymous variants, one nonsense, one start codon variant, and one inframe indel were detected. Among them, a nonsense LRP12 mutation was classified as pathogenic according to ACMG guidelines. However, none of the variants were considered disease-causing according to in-silico predictions.Conclusions:Increased number or mutational burden of DMNs are not observed in Chinese patients with microtia. DMNs is not the primary cause of microtia, although rare DNMs in responsible genes could occasionally lead to cases.

OBJECTIVE: To screen for LDLR gene mutations in 9 patients with familial hypercholesterolemia (FH). METHODS: All exons of the LDLR gene and flanking intronic sequences were amplified by PCR and subjected to automatic DNA sequencing. For patients with homozygous or compound heterozygous mutations, parental DNA sequencing or T cloning sequencing was carried out to determine the parental origin of the mutant alleles. RESULTS: Direct sequencing of PCR products revealed 8 LDLR variants in 7 patients, which included c.259T>G, c.513delC, c.530C>T, c.682G>T, c.763C>T, c.1187-10G>A, c.1948delG, and c.1730G>A, among which c.1948delG was novel. Four patients have carried heterozygous mutations, two carried homozygous mutations, and one carried compound heterozygous mutations. The patients with biallelic mutations presented with a more severe phenotype compared those carrying heterozygous mutations. CONCLUSION LDLR mutations were identified in 7 out of 9 patients with FH. Among the 8 identified LDLR mutations, c.1948delG was firstly reported. Above findings have expanded the mutation spectrum of LDLR gene.
DNA Mutational Analysis ; Genetic Testing ; Humans ; Hyperlipoproteinemia Type II ; genetics ; Mutation ; Phenotype ; Receptors, LDL ; genetics

OBJECTIVETo organize the clinical practice guidelines (CPGs) related to acupuncture included in the National Guideline Clearinghouse (NGC) to systematically summarize the diseases and disorders most commonly treated with acupuncture, the strength of recommendations for acupuncture and the quality of evidence.

METHODSThe NGC database was systematically searched for guidelines that included acupuncture as an intervention. Two independent reviewers studied the summaries and the full texts of the guidelines and included guidelines based on the inclusion and exclusion criteria. Thirty-nine guidelines were collected with 80 recommendations. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument was used to assess the quality of these guidelines.

RESULTSOf the 80 recommendations on acupuncture, 49 recommendations were clearly for acupuncture, 25 recommendations were against acupuncture and 6 recommendations did not indicate any clear recommendations, 37 recommendations were for painful diseases/disorders, and 12 recommendations were for non-painful diseases/disorders. Locomotor system disorders were the most common in the painful diseases/disorders category. Out of all the recommendations for acupuncture, most recommendations (87.76%) were weak in strength, and most of the evidence (40.84%) was of low quality.

CONCLUSIONSIn the National Guideline Clearinghouse, the recommendations for acupuncture focus on painful diseases/disorders. The recommendations in the guidelines are not high in strength, and most of the evidence is moderate or low in quality.

Objective To investigate the differences in platelet and platelet parameters between patients with different types and etiologies of acute-on-chronic liver failure (ACLF) and the influence of platelet and its dynamic change on the prognosis of ACLF patients. Methods Clinical data, liver function parameters, platelet, and platelet parameters were collected from 364 patients with ACLF who attended Tianjin Third Central Hospital from January 2014 to December 2018. Platelet level and platelet parameters (platelet distribution width and mean platelet volume) were compared between the patients with different types and etiologies of ACLF, and their influence on the 90-day mortality rate of ACLF patients was analyzed, as well as the association of the dynamic change of platelet at baseline and on days 7 and 14 after admission with the prognosis of patients. The chi-square test was used for comparison of categorical data between groups; the Kruskal-Wallis H test or Mann-Whitney U test was used for comparison of continuous data between groups; the Kaplan-Meier method was used for survival analysis; the univariate and multivariate Cox regression analyses were used to analyze the parameters associated with prognosis; the repeated measures analysis of variance was used to analyze the dynamic change of platelet; receiver operating characteristic (ROC) curve was plotted based on platelet level and overall survival. Results The patients with type C ACLF had a significantly lower platelet level than those with type A/B ACLF (all P < 0.001). Compared with the ACLF patients with hepatitis B, the ACLF patients with autoimmune liver diseases had a significant reduction in mean platelet volume ( P =0.035). Based on the cut-off value obtained by the ROC curve analysis, the patients with a platelet level of < 60.5×10 9 /L had a significantly higher mortality rate than those with a platelet level of ≥60.5×10 9 /L ( P =0.006). Platelet level was an independent protective factor against 90-day death in ACLF patients (hazard ratio=0.995, 95% confidence interval: 0.990-0.999, P =0.026), and the mortality rate increased with the reduction in platelet level. The patients with type C ACLF had a significantly higher mortality rate than those with type A ACLF ( P < 0.05), and the death group tended to have a significantly greater reduction in platelet level ( P < 0.05). Compared with the survival group, the 90-day death group had a significantly greater reduction in platelet ( P =0.032). Conclusion There is a difference in platelet level between ACLF patients with different types. Platelet level is an important indicator for the 90-day prognosis of ACLF patients, and patients with a greater dynamic reduction in platelet tend to have a higher 90-day mortality rate.

Humans ; Goldenhar Syndrome ; Phenotype ; Mutation ; DNA-Binding Proteins/genetics* ; Protein Tyrosine Phosphatases/genetics* ; Peptide Elongation Factors/genetics* ; Ribonucleoprotein, U5 Small Nuclear/genetics*

BACKGROUNDMedullary cystic kidney disease (MCKD) is clinically indistinguishable from several other autosomal-dominant renal diseases; thus, molecular genetic testing is needed to establish a definitive diagnosis. A specific type of single cytosine insertion in the variable number tandem repeat (VNTR) of the mucin 1 (MUC1) gene is the only known cause of MCKD1; however, genetic analysis of this mutation is difficult and not yet offered routinely. To identify the causative mutation/s and establish a definitive diagnosis in a Chinese family with chronic kidney disease, clinical assessments and genetic analysis were performed, including using a modified genotyping method to identify the MUC1- VNTR single cytosine insertion.

METHODSClinical data from three patients in a Chinese family with chronic kidney disease were collected and evaluated. Linkage analysis was used to map the causative locus. Mutation analysis of uromodulin (UMOD) gene was performed using polymerase chain reaction (PCR) and direct sequencing. For MUC1 genotyping, the mutant repeat units were enriched by MwoI restriction, and then were amplified and introduced into pMD-18T vectors. The 192 clones per transformant were picked up and tested by colony PCR and second round of MwoI digestion. Finally, Sanger sequencing was used to confirm the MUC1 mutation.

RESULTSClinical findings and laboratory results were consistent with a tubulointerstitial lesion. Linkage analysis indicated that the family was compatible with the MCKD1 locus. No mutations were found in UMOD gene. Using the modified MUC1 genotyping method, we detected the MUC1-VNTR single cytosine insertion events in three patients of the family; and mutation-containing clones were 12/192, 14/192, and 5/96, respectively, in the three patients.

CONCLUSIONSClinical and genetic findings could support the MCKD1 diagnosis. The modified strategy has been demonstrated to be a practical way to detect MUC1 mutation.