BMC Medical Genetics最新文献

{"title":"Association of PNPLA3 rs738409 G/C gene polymorphism with nonalcoholic fatty liver disease in children: a meta-analysis.","authors":"Shan Tang,&nbsp;Jing Zhang,&nbsp;Ting Ting Mei,&nbsp;Hai Qing Guo,&nbsp;Xin Huan Wei,&nbsp;Wen Yan Zhang,&nbsp;Ya Li Liu,&nbsp;Shan Liang,&nbsp;Zuo Peng Fan,&nbsp;Li Xia Ma,&nbsp;Wei Lin,&nbsp;Yi Rong Liu,&nbsp;Li Xia Qiu,&nbsp;Hai Bin Yu","doi":"10.1186/s12881-020-01098-8","DOIUrl":"https://doi.org/10.1186/s12881-020-01098-8","url":null,"abstract":"<p><strong>Background: </strong>Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Current studies have shown that PNPLA3 (Patatin-like phospholipase domain containing 3) rs738409 G/C gene polymorphism is associated with adult nonalcoholic fatty liver disease [1, 2].But there is no consensus on the relationship between PNPLA3 rs738409 G/C gene polymorphism and children NAFLD due to differences in population samples. To this end, a meta-analysis of published research is conducted to comprehensively assess the relationship between PNPLA3 gene polymorphism and NAFLD in children.</p><p><strong>Methods: </strong>We searched MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to May 2019. Case-control studies assessing the relationship between PNPLA3 rs738409 G/C gene polymorphism with non-alcoholic fatty liver disease in children were selected according to inclusion and exclusion criteria. Random effects model was used to quantify the association between the PNPLA3 rs738409 G/C gene polymorphism and the susceptibility of children's NAFLD. Fixed effects model was used to quantify the relationship between the PNPLA3 rs738409 G/C gene polymorphism and the severity of NAFLD in children. The Stata 12.0 software was employed for data analysis.</p><p><strong>Results: </strong>A total of nine case-control studies were included in this meta-analysis containing data of 1173 children with NAFLD and 1792 healthy controls. Five studies compared NAFLD children and non-NAFLD healthy populations. Statistical analysis showed that PNPLA3 gene polymorphism was significantly associated with children's NAFLD in the allele contrast, dominant, recessive and over dominant models (G vs C,OR = 3.343, 95% CI = 1.524-7.334; GG + GC vs CC,OR = 3.157, 95% CI = 1.446-6.892;GG vs GC + CC,OR = 5.692, 95% CI = 1.941-16.689; GG + CC vs GC,OR = 2.756, 95% CI = 1.729-4.392). Four case-control studies compared Children with nonalcoholic fatty liver (NAFL) and children with nonalcoholic steatohepatitis (NASH). The results showed that the PNPLA3 gene polymorphism was also significantly associated with the severity of NAFLD in children in recessive gene model (GG vs GC + CC,OR = 14.43, 95% CI = 5.985-34.997); The Egger's test revealed no significant publication bias.</p><p><strong>Conclusions: </strong>Meta-analysis showed that PNPLA3 gene polymorphism was significantly associated with susceptibility and severity of NAFLD in children.</p>","PeriodicalId":9015,"journal":{"name":"BMC Medical Genetics","volume":" ","pages":"163"},"PeriodicalIF":0.0,"publicationDate":"2020-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12881-020-01098-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38276247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin receptor gene polymorphisms c.668A>G and c.1968G>C in Sudanese women with preeclampsia: a case-control study.","authors":"Amira Saad,&nbsp;Ishag Adam,&nbsp;Salah Eldin G Elzaki,&nbsp;Hiba A Awooda,&nbsp;Hamdan Z Hamdan","doi":"10.1186/s12881-020-01104-z","DOIUrl":"https://doi.org/10.1186/s12881-020-01104-z","url":null,"abstract":"<p><strong>Background: </strong>Leptin receptor gene (LEPR) variants may affect the leptin levels and act as a risk factor for preeclampsia. Two LEPR gene missense variants rs1137101 (c.668A>G) and rs1805094 (c.1968G>C) were investigated in Sudanese women with preeclampsia.</p><p><strong>Methods: </strong>A matched case-control study (122 women in each arm) was conducted in Saad Abualila Maternity Hospital in Khartoum, Sudan from May to December 2018. The cases were women with preeclampsia and the controls were healthy pregnant women. Genotyping for LEPR gene variants c.668A>G and c.1968G>C was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models (adjusted for age, parity, body mass index and hemoglobin level) were conducted.</p><p><strong>Results: </strong>Genotype frequency of LEPR gene variants c.668A>G and c.1968G>C was in accordance with Hardy-Weinberg equilibrium (P > 0.05) in the controls. Allele G in LEPRc.668A>G variant was significantly more frequent in the cases compared with the controls [43.4% vs. 10.2%; OR = 6.44; 95%CI (3.98-10.40); P < 0.001]. In variant LEPRc.668A>G, genotype AG was the prevalent genotype in the cases compared with the controls, and it was significantly associated with preeclampsia risk [37.7% vs. 15.5%; AOR = 3.48; 95%CI (1.15-10.54); P = 0.027]. Likewise, the GG genotype was the second most common genotype in the cases compared with the controls, and was associated with preeclampsia risk [24.6% vs. 2.5%; AOR = 14.19; 95%CI (1.77-113.76); P = 0.012]. None of the LEPRc.1968G>C variant genotypes were associated with preeclampsia. The CC genotype was not detected in neither the cases nor the controls. The haplotype A-G 70.1% was the prevalent haplotype in this population, and it significantly protected against preeclampsia [OR = 0.14; 95%CI (0.09-0.23); P < 0.001]. However, the haplotype G-G 26.8% was significantly associated with preeclampsia risk [OR = 6.70; 95%CI (4.16-11.05); P < 0.001]. Both variants c.668A>G and c.1968G>C were in strong linkage disequilibrium (D' = 1, r² = 0.012).</p><p><strong>Conclusions: </strong>Our data indicate that the rs1137101 (c.668A>G) variant and G-G haplotype may independently associate with the development of preeclampsia.</p>","PeriodicalId":9015,"journal":{"name":"BMC Medical Genetics","volume":" ","pages":"162"},"PeriodicalIF":0.0,"publicationDate":"2020-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12881-020-01104-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38274553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report expanding the germline AXIN2- related phenotype to include olfactory neuroblastoma and gastric adenoma.","authors":"Sarah K Macklin-Mantia,&nbsp;Stephanie L Hines,&nbsp;Kaisorn L Chaichana,&nbsp;Angela M Donaldson,&nbsp;Stephen L Ko,&nbsp;Qihui Zhai,&nbsp;Niloy Jewel Samadder,&nbsp;Douglas L Riegert-Johnson","doi":"10.1186/s12881-020-01103-0","DOIUrl":"https://doi.org/10.1186/s12881-020-01103-0","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic AXIN2 variants cause absence of permanent teeth (hypodontia), sparse hair and eye brows (ectodermal dysplasia), and gastrointestinal polyps and cancer. Inheritance is autosomal dominant with variable penetrance. Only twenty- five patients have been reported from five families. A Mayo Clinic pilot program tested 3009 newly diagnosed cancer patients for pathogenic germline variants in 83 hereditary cancer genes, including AXIN2. We found only one patient with a pathogenic AXIN2 variant.</p><p><strong>Case presentation: </strong>The proband was a 49 year-old female who came to Otolaryngology clinic complaining of right-sided nasal obstruction. Biopsy of identified nasal polyp revealed olfactory neuroblastoma (esthesioneuroblastoma). Surgical resection with gross, total tumor resection was followed by radiation therapy. The patient enrolled in a clinical pilot of genetic testing and a pathogenic variant in AXIN2, c.1822del (p.Leu608Phefs*81) (NM_004655.3) was found. She was seen in Medical Genetics clinic and found to have a personal history of hypodontia. Her eyebrows, hair, and nails were all normal. She underwent upper endoscopy and colonoscopy. A four mm gastric adenoma was found and removed.</p><p><strong>Conclusions: </strong>This is the first case reported on a patient with a pathogenic, germline AXIN2 variant and an olfactory neuroblastoma or a gastric adenoma. We propose that these could be features of the AXIN2 phenotype. The known association between gastric adenomas and familial adenomatous polyposis, the other Wnt/beta-catenin disorder, supports the hypothesis that pathogenic AXIN2 variants increase risk as well. As the odds of a chance co-occurrence of a pathogenic AXIN2 variant and an olfactory neuroblastoma are so rare, it is worth exploring potential causation. We are building a clinical registry to expand understanding of the AXIN2 phenotype and request any clinicians caring for patients with pathogenic AXIN2 variants to contact us.</p>","PeriodicalId":9015,"journal":{"name":"BMC Medical Genetics","volume":" ","pages":"161"},"PeriodicalIF":0.0,"publicationDate":"2020-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12881-020-01103-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38283388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of MC4R (rs17782313) with diabetes and cardiovascular disease in Korean men and women.","authors":"Jae Woong Sull,&nbsp;Gitae Kim,&nbsp;Sun Ha Jee","doi":"10.1186/s12881-020-01100-3","DOIUrl":"https://doi.org/10.1186/s12881-020-01100-3","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is mostly assessed by the fasting glucose level. Several studies reported that serum fasting glucose levels and cardiovascular disease are associated with MC4R.</p><p><strong>Methods: </strong>A total of 4294 subjects participated in this study. There were 1810 subjects with cardiovascular disease among the 4294 subjects. We used multivariate linear regression models and multiple logistic regression analysis.</p><p><strong>Results: </strong>Individuals with the TC/CC genotype had a 1.29-fold higher risk of diabetes than did those with the TT genotype when adjusting for age, sex, and BMI (OR, 1.29; 95% CI, 1.04-1.60). For healthy subjects, the association was significant in women (OR, 1.99; 95% CI, 1.01-3.93). Men with the TC/CC genotype had a 1.21-fold higher risk of cardiovascular disease than did those with the TT genotype when adjusting for age, sex, and BMI (OR, 1.21; 95% CI, 1.04-1.41). The relationship between MC4R and cardiovascular disease was stronger in lean men (OR, 1.40; 95% CI, 1.12-1.74, p = 0.0028) than in overweight men.</p><p><strong>Conclusions: </strong>This study suggests that the rs17782313 SNP in MC4R is related to diabetes and the SNP is also associated with cardiovascular disease in lean men.</p>","PeriodicalId":9015,"journal":{"name":"BMC Medical Genetics","volume":" ","pages":"160"},"PeriodicalIF":0.0,"publicationDate":"2020-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12881-020-01100-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38282819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome-wide supported CACNA1C gene polymorphisms and the risk of schizophrenia: an updated meta-analysis.","authors":"Yong-Ping Liu,&nbsp;Xue Wu,&nbsp;Xi Xia,&nbsp;Jun Yao,&nbsp;Bao-Jie Wang","doi":"10.1186/s12881-020-01084-0","DOIUrl":"https://doi.org/10.1186/s12881-020-01084-0","url":null,"abstract":"<p><strong>Background: </strong>The CACNA1C gene was defined as a risk gene for schizophrenia in a large genome-wide association study of European ancestry performed by the Psychiatric Genomics Consortium. Previous meta-analyses focused on the association between the CACNA1C gene rs1006737 and schizophrenia. The present study focused on whether there was an ancestral difference in the effect of the CACNA1C gene rs1006737 on schizophrenia. rs2007044 and rs4765905 were analyzed for their effect on the risk of schizophrenia.</p><p><strong>Methods: </strong>Pooled, subgroup, sensitivity, and publication bias analysis were conducted.</p><p><strong>Results: </strong>A total of 18 studies met the inclusion criteria, including fourteen rs1006737 studies (15,213 cases, 19,412 controls), three rs2007044 studies (6007 cases, 6518 controls), and two rs4765905 studies (2435 cases, 2639 controls). An allele model study also related rs2007044 and rs4765905 to schizophrenia. The overall meta-analysis for rs1006737, which included the allele contrast, dominant, recessive, codominance, and complete overdominance models, showed significant differences between rs1006737 and schizophrenia. However, the ancestral-based subgroup analysis for rs1006737 found that the genotypes GG and GG + GA were only protective factors for schizophrenia in Europeans. In contrast, the rs1006737 GA genotype only reduced the risk of schizophrenia in Asians.</p><p><strong>Conclusions: </strong>Rs1006737, rs2007044, and rs4765905 of the CACNA1C gene were associated with susceptibility to schizophrenia. However, the influence model for rs1006737 on schizophrenia in Asians and Europeans demonstrated both similarities and differences between the two ancestors.</p>","PeriodicalId":9015,"journal":{"name":"BMC Medical Genetics","volume":" ","pages":"159"},"PeriodicalIF":0.0,"publicationDate":"2020-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12881-020-01084-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38243328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual molecular diagnosis of tricho-rhino-phalangeal syndrome type I and Okur-Chung neurodevelopmental syndrome in one Chinese patient: a case report.","authors":"Shanshan Xu,&nbsp;Qun Lian,&nbsp;Jinzhun Wu,&nbsp;Lingli Li,&nbsp;Jia Song","doi":"10.1186/s12881-020-01096-w","DOIUrl":"https://doi.org/10.1186/s12881-020-01096-w","url":null,"abstract":"<p><strong>Background: </strong>Okur-Chung neurodevelopmental syndrome (OCNDS) and tricho-rhino-phalangeal syndrome type I (TRPSI) are rare Mendelian diseases. OCNDS is caused by CSNK2A1 gene variants and TRPSI is caused by the TRPS1gene. However, to have two Mendelian diseases in one patient is even rarer.</p><p><strong>Case presentation: </strong>A 6-year-10-month-old boy characterized by special facial features, short stature and mental retardation was referred to our pediatric endocrinology department. Whole-exome sequencing (WES) was done to detect the molecular basis of his disease. This patient was confirmed to carry two variants in the CSNK2A1 gene and one in the TRPS1 gene. The variant in the CSNK2A1 gene was vertically transmitted from his father, and the variant in TRPS1 gene from his mother. These two variants are classified as pathogenic and the causes of the presentation in this child. This patient's father and mother have subsequently been diagnosed as having OCNDS and TRPSI respectively.</p><p><strong>Conclusion: </strong>This is the first reported case of a dual molecular diagnosis of tricho-rhino-phalangeal syndrome type I and Okur-Chung neurodevelopmental syndrome in the same patient. This patient is the first published example of vertical transmission of this recurrent CSN2A1 variant from parent to child. A novel variant in the TRPS1 gene that is pathogenic was also identified. In conclusion, identification of the variants in this patient expands the phenotypes and molecular basis of dual Mendelian diseases.</p>","PeriodicalId":9015,"journal":{"name":"BMC Medical Genetics","volume":" ","pages":"158"},"PeriodicalIF":0.0,"publicationDate":"2020-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12881-020-01096-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38231371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence.","authors":"Yunxiao Li,&nbsp;Yongsheng Zhu,&nbsp;Jianghua Lai,&nbsp;Xugang Shi,&nbsp;Yuanyuan Chen,&nbsp;Jinyu Zhang,&nbsp;Shuguang Wei","doi":"10.1186/s12881-020-01092-0","DOIUrl":"https://doi.org/10.1186/s12881-020-01092-0","url":null,"abstract":"<p><strong>Background: </strong>Heroin dependence is a complex disease with multiple phenotypes. Classification of heroin users into more homogeneous subgroups on the basis of these phenotypes could help to identify the involved genetic factors and precise treatments. This study aimed to identify the association between genetic polymorphisms of DA synthesis and metabolism genes, including tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), solute carrier family 6 member 3 (SLC6A3) and DA beta-hydroxylase (DBH), with six important phenotypes of heroin dependence.</p><p><strong>Methods: </strong>A total of 801 heroin dependent patients were recruited and fourteen potential functional single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot. Associations between SNPs with six phenotypes were mainly assessed by binary logistic regression. Generalized multifactor dimensionality reduction was used to analyze the gene-by-gene and gene-by-environment interactions.</p><p><strong>Results: </strong>We found that DBH rs1611114 TT genotype had a protective effect on memory impairment after heroin dependence (P = 0.002, OR = 0.610). We also found that the income-rs12666409-rs129915-rs1611114 interaction yielded the highest testing balance accuracy and cross-validation consistency for memory change after heroin dependence.</p><p><strong>Conclusions: </strong>Our results suggest that the memory change after heroin dependence was a result of a combination of genetics and environment. This finding could lead to a better understanding of heroin dependence and further improve personalized treatment.</p>","PeriodicalId":9015,"journal":{"name":"BMC Medical Genetics","volume":" ","pages":"157"},"PeriodicalIF":0.0,"publicationDate":"2020-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12881-020-01092-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38213805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, biochemical, and genetic analysis of a Chinese Han pedigree with holocarboxylase synthetase deficiency: a case report.","authors":"Zhenzhu Zheng,&nbsp;Gaopin Yuan,&nbsp;Minyan Zheng,&nbsp;Yiming Lin,&nbsp;Faming Zheng,&nbsp;Mengyi Jiang,&nbsp;Lin Zhu,&nbsp;Qingliu Fu","doi":"10.1186/s12881-020-01080-4","DOIUrl":"https://doi.org/10.1186/s12881-020-01080-4","url":null,"abstract":"<p><strong>Background: </strong>Holocarboxylase synthetase (HLCS) deficiency is a rare inborn disorder of biotin metabolism, which results in defects in several biotin-dependent carboxylases and presents with metabolic ketoacidosis and skin lesions.</p><p><strong>Case presentation: </strong>In this paper, we report a Chinese Han pedigree with HLCS deficiency diagnosed by using next-generation sequencing and validated with Sanger sequencing of the HLCS and BTD genes. The Chinese proband carries the common missense mutation c.1522C > T (p.Arg508Trp) in exon 9 of the HLCS gene, which generates an increased K_m value for biotin. A novel frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15) in exon 6 of the HLCS gene is predicted to be deleterious through PROVEAN and MutationTaster. A novel heterozygous mutation, c.638_642delAACAC (p.His213Profs*4), in the BTD gene is also identified.</p><p><strong>Conclusions: </strong>The Chinese proband carries the reported Arg508Trp variant, the novel 2-bp frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15), which expands the mutational spectrum of the HLCS gene, and the novel heterozygous mutation c.638_642delAACAC (p.His213Profs*4), which expands the mutational spectrum of the BTD gene. Furthermore, reversible hearing damage is rarely reported in patients with HLCS deficiency, which deserves further discussion.</p>","PeriodicalId":9015,"journal":{"name":"BMC Medical Genetics","volume":" ","pages":"155"},"PeriodicalIF":0.0,"publicationDate":"2020-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12881-020-01080-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38214463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel MYH14 mutation in a Chinese family with autosomal dominant nonsyndromic hearing loss.","authors":"Mingming Wang,&nbsp;Yicui Zhou,&nbsp;Fengguo Zhang,&nbsp;Zhaomin Fan,&nbsp;Xiaohui Bai,&nbsp;Haibo Wang","doi":"10.1186/s12881-020-01086-y","DOIUrl":"https://doi.org/10.1186/s12881-020-01086-y","url":null,"abstract":"<p><strong>Background: </strong>MYH14 gene mutations have been suggested to be associated with nonsyndromic/syndromic sensorineural hearing loss. It has been reported that mutations in MYH14 can result in autosomal dominant nonsyndromic deafness-4A (DFNA4).</p><p><strong>Methods: </strong>In this study, we examined a four-generation Han Chinese family with nonsyndromic hearing loss. Targeted next-generation sequencing of deafness genes was employed to identify the pathogenic variant. Sanger sequencing and PCR-RFLP analysis were performed in affected members of this family and 200 normal controls to further confirm the mutation.</p><p><strong>Results: </strong>Four members of this family were diagnosed as nonsyndromic bilateral sensorineural hearing loss with postlingual onset and progressive impairment. A novel missense variant, c.5417C > A (p.A1806D), in MYH14 in the tail domain of NMH II C was successfully identified as the pathogenic cause in three affected individuals. The family member II-5 was suggested to have noise-induced deafness.</p><p><strong>Conclusion: </strong>In this study, a novel missense mutation, c.5417C > A (p.A1806D), in MYH14 that led to postlingual nonsyndromic autosomal dominant SNHL were identified. The findings broadened the phenotype spectrum of MYH14 and highlighted the combined application of gene capture and Sanger sequencing is an efficient approach to screen pathogenic variants associated with genetic diseases.</p>","PeriodicalId":9015,"journal":{"name":"BMC Medical Genetics","volume":" ","pages":"154"},"PeriodicalIF":0.0,"publicationDate":"2020-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12881-020-01086-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38200107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe syndromic ID and skewed X-inactivation in a girl with NAA10 dysfunction and a novel heterozygous de novo NAA10 p.(His16Pro) variant - a case report.","authors":"Ingrid Bader, Nina McTiernan, Christine Darbakk, Eugen Boltshauser, Rasmus Ree, Sabine Ebner, Johannes A Mayr, Thomas Arnesen","doi":"10.1186/s12881-020-01091-1","DOIUrl":"10.1186/s12881-020-01091-1","url":null,"abstract":"<p><strong>Background: </strong>NAA10 is the catalytic subunit of the major N-terminal acetyltransferase complex NatA which acetylates almost half the human proteome. Over the past decade, many NAA10 missense variants have been reported as causative of genetic disease in humans. Individuals harboring NAA10 variants often display variable degrees of intellectual disability (ID), developmental delay, and cardiac anomalies. Initially, carrier females appeared to be oligo- or asymptomatic with X-inactivation pattern skewed towards the wild type allele. However, recently it has been shown that NAA10 variants can cause syndromic or non-syndromic intellectual disability in females as well. The impact of specific NAA10 variants and the X-inactivation pattern on the individual phenotype in females remains to be elucidated.</p><p><strong>Case presentation: </strong>Here we present a novel de novo NAA10 (NM_003491.3) c.[47A > C];[=] (p.[His16Pro];[=]) variant identified in a young female. The 10-year-old girl has severely delayed motor and language development, disturbed behavior with hyperactivity and restlessness, moderate dilatation of the ventricular system and extracerebral CSF spaces. Her blood leukocyte X-inactivation pattern was skewed (95/5) towards the maternally inherited X-chromosome. Our functional study indicates that NAA10 p.(H16P) impairs NatA complex formation and NatA catalytic activity, while monomeric NAA10 catalytic activity appears to be intact. Furthermore, cycloheximide experiments show that the NAA10 H16P variant does not affect the cellular stability of NAA10.</p><p><strong>Discussion and conclusions: </strong>We demonstrate that NAA10 p.(His16Pro) causes a severe form of syndromic ID in a girl most likely through impaired NatA-mediated Nt-acetylation of cellular proteins. X-inactivation analyses showed a skewed X-inactivation pattern in DNA from blood of the patient with the maternally inherited allele being preferentially methylated/inactivated.</p>","PeriodicalId":9015,"journal":{"name":"BMC Medical Genetics","volume":" ","pages":"153"},"PeriodicalIF":0.0,"publicationDate":"2020-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38183433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}