Annals of Human Genetics最新文献

筛选
英文 中文
Attitude toward personal genomics: A nation-wide survey of public and professionals in Pakistan 对个人基因组学的态度:巴基斯坦公众和专业人士的全国性调查
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2021-03-30 DOI: 10.1111/ahg.12419
Muhammad Ilyas, Saima Malik, Mukhtar Alam, Aamir Mahmood, Muhammad Irfan, Muttahid Shah, Atiqur Rahman, Habib Ahmad
{"title":"Attitude toward personal genomics: A nation-wide survey of public and professionals in Pakistan","authors":"Muhammad Ilyas,&nbsp;Saima Malik,&nbsp;Mukhtar Alam,&nbsp;Aamir Mahmood,&nbsp;Muhammad Irfan,&nbsp;Muttahid Shah,&nbsp;Atiqur Rahman,&nbsp;Habib Ahmad","doi":"10.1111/ahg.12419","DOIUrl":"10.1111/ahg.12419","url":null,"abstract":"<p>With the emergence of modern genetic testing and profiling techniques, it has become imperative to assess the general public awareness and attitudes toward such developments. The public's perspective and possible responses are necessary for planning commercial, legal, medical, or healthcare initiatives. The purpose of this study was to assess the perception of the general public and professionals about the personal genome testing and genetic profiling. A questionnaire-based survey was conducted to investigate the attitudes of 2954 adults (56.4% male and 43.6% female) from more than 120 different educational, research, and professional organizations of Pakistan. The aim of the study was to assess interest in genomic testing. The findings of this survey will feed into the larger Genome Projects in Pakistan and will be helpful for the national bioethical committee, healthcare agencies, diagnostic companies, and other institutions for making policy decisions.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"85 5","pages":"196-199"},"PeriodicalIF":1.9,"publicationDate":"2021-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/ahg.12419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25541518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hydrops fetalis in PKD1L1-related heterotaxy: Report of two foetuses and expanding the phenotypic and molecular spectrum pkd1l1相关异位的水肿胎儿:两个胎儿的报告和扩大表型和分子谱
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2021-03-02 DOI: 10.1111/ahg.12417
Alec Reginald Errol Correa, Mounika Endrakanti, Kamal Naini, Madhulika Kabra, Neerja Gupta
{"title":"Hydrops fetalis in PKD1L1-related heterotaxy: Report of two foetuses and expanding the phenotypic and molecular spectrum","authors":"Alec Reginald Errol Correa,&nbsp;Mounika Endrakanti,&nbsp;Kamal Naini,&nbsp;Madhulika Kabra,&nbsp;Neerja Gupta","doi":"10.1111/ahg.12417","DOIUrl":"10.1111/ahg.12417","url":null,"abstract":"<p>Abnormalities in the normal left–right axis asymmetry range from situs inversus totalis to situs ambiguous or heterotaxy. More than 80 genes have been described to have a role in the establishment of the normal situs of the internal organs. Pathogenic variants in the <i>PKD1L1</i> gene have recently been described in heterotaxy and congenital heart disease. Till date, 11 families have been described with <i>PKD1L1-</i>related heterotaxy. We describe the first Indian family with two affected foetuses with <i>PKD1L1</i>-related nonimmune hydrops, congenital heart disease, situs inversus, and heterotaxy, with biallelic variants in the compound heterozygous state.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"85 3-4","pages":"138-145"},"PeriodicalIF":1.9,"publicationDate":"2021-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/ahg.12417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25431329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Crosstalk between miR-203 and PKCθ regulates breast cancer stem cell markers miR-203和PKCθ之间的串扰调节乳腺癌干细胞标记物
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2021-02-12 DOI: 10.1111/ahg.12415
Sohair Salem, Rehab Mosaad
{"title":"Crosstalk between miR-203 and PKCθ regulates breast cancer stem cell markers","authors":"Sohair Salem,&nbsp;Rehab Mosaad","doi":"10.1111/ahg.12415","DOIUrl":"10.1111/ahg.12415","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Protein kinase C theta (PKCθ) is expressed in ER-negative breast cancer and promotes cancer stem cells (CSCs) phenotype. PKCθ gene (<i>PRKCQ</i>) is predicted to be a target for tumor suppressor <i>miR-203</i>. Herein, we aim to validate this prediction and evaluate the ability of <i>miR-203</i> to inhibit migration of breast cancer cell line enriched with CSCs, MDA-MB-231, via <i>PRKCQ</i> targeting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cells were transfected with <i>miR-203</i> mimic, <i>PRKCQ</i> siRNA and negative control; then real-time PCR, migration assay, western blotting, reporter assay, and chromatin accessibility assay were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings displayed significant decrease in <i>PRKCQ</i> mRNA level and luciferase signals in cells with restored <i>miR-203</i> expression, therefore, validated <i>PRKCQ</i> as a direct target of <i>miR-203</i>. Additionally, inhibiting <i>PRKCQ</i> by siRNA led to significant inhibition of <i>miR-203</i> expression and significant decrease of chromatin accessibility at <i>miR-203</i> promoter region 466–291 upstream TSS. Both of <i>miR-203</i> re-expression and <i>PRKCQ</i> suppression resulted in altering migration ability of MDA-MB-231 through regulating AKT pathway and genes involved in breast cancer stem cells, <i>CD44</i> and <i>ALDH1A3</i>. Expression of <i>CDK5</i>, <i>GIV</i>, and <i>NANOG</i> was significantly downregulated in <i>miR-203</i> mimic-transfected cells, while <i>PRKCQ</i> siRNA-transfected cells displayed downregulation of <i>OCT3/4</i>, <i>SOX2</i>, and <i>NANOG</i>. Furthermore, we found that <i>miR-224</i> expression was enhanced while <i>miR-150</i> was downregulated after ectopic expression of <i>miR-203</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study highlighted the negative feedback loop between <i>miR-203</i> and its target <i>PRKCQ</i> and the interplay between them in regulating genes involved in BCSCs. The study also concluded “microRNA-mediated microRNA regulation” as an event in breast cancer cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"85 3-4","pages":"105-114"},"PeriodicalIF":1.9,"publicationDate":"2021-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/ahg.12415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25364260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Genetics background of β-thalassemia (3.5 kb deletion) in Southern Thailand: Haplotype analysis using novel reverse dot blot hybridization 泰国南部β-地中海贫血(3.5 kb缺失)的遗传背景:使用新型反向斑点杂交进行单倍型分析
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2021-02-08 DOI: 10.1111/ahg.12416
Wanicha Tepakhan, Korntip Srewaradachpisal, Sataron Kanjanaopas, Wittaya Jomoui
{"title":"Genetics background of β-thalassemia (3.5 kb deletion) in Southern Thailand: Haplotype analysis using novel reverse dot blot hybridization","authors":"Wanicha Tepakhan,&nbsp;Korntip Srewaradachpisal,&nbsp;Sataron Kanjanaopas,&nbsp;Wittaya Jomoui","doi":"10.1111/ahg.12416","DOIUrl":"10.1111/ahg.12416","url":null,"abstract":"<p>β-thalassemia (β-thal) (3.5 kb deletion or NC_000011.10:g.5224302-5227791del3490bp) is a common mutation in southern Thailand. This study aimed to determine genetic diversity in subjects with β-thal (3.5 kb deletion) alleles and to ascertain the origin of this mutation using haplotype and phylogenetic analysis. The study was carried out on members of the southern Thai population, including 45 normal individuals, 116 heterozygous β-thal (3.5 kb deletion) and one homozygous β-thal (3.5 kb deletion). The 5′-haplotype in β-globin gene cluster was examined using newly developed reverse dot blot hybridization (RDB) and compared with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed 100% concordance between the haplotype patterns of these two methods. From a total of 324 chromosomes, nine haplotypes were segregated. Haplotype H2 (+ – – – –) was the predominant haplotype observed in all 118 β-thal (3.5 kb deletion) chromosomes, which revealed a single origin. The phylogenetic tree demonstrated that β-thal (3.5 kb deletion) has an older genetic defect in this region. Moreover, the developed RDB is simple, less time-consuming, inexpensive, and does not restriction enzyme digestion.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"85 3-4","pages":"115-124"},"PeriodicalIF":1.9,"publicationDate":"2021-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/ahg.12416","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25347833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Atrioventricular canal defect is the classic congenital heart disease in Bardet–Biedl syndrome 房室管缺损是Bardet-Biedl综合征的典型先天性心脏病
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2021-01-12 DOI: 10.1111/ahg.12413
Flaminia Pugnaloni, Paolo Versacci, Bruno Marino, Maria Cristina Digilio
{"title":"Atrioventricular canal defect is the classic congenital heart disease in Bardet–Biedl syndrome","authors":"Flaminia Pugnaloni,&nbsp;Paolo Versacci,&nbsp;Bruno Marino,&nbsp;Maria Cristina Digilio","doi":"10.1111/ahg.12413","DOIUrl":"10.1111/ahg.12413","url":null,"abstract":"To the Editor, We read with great interest the recent study of Gumus, Tuncez, Oz, and Guvenc (2020), who performed exome sequencing analysis in individuals diagnosed of Bardet– Biedl (BBS) and reported an atrioventricular canal defect (AVCD) in a patient carrying a silent LZTFL1 variant. LZTFL1 (BBS17) encodes a ubiquitously expressed protein that interacts with BBS protein complexes and acts as an important negative regulator of BBSome ciliary trafficking and Sonic hedgehog (Shh) signaling. In the discussion, the authors state that AVCD is a very rare cardiac anomaly among BBS patients.Wewould like to point out that AVCD and laterality defects are important and not so rare features in BBS. Cardiac involvement in BBS has originally been described as aortic valve anomalies (aortic stenosis), atrial septal defect, pulmonary stenosis, and dilated cardiomyopathy. However, these clinical observations were made before most BBS genes were discovered. In parallel to the molecular advances in defining BBS, cardiac phenotype was also better characterized. Reviews of BBS case series and of overlapping syndromes (i.e., BBS–McKusick– Kaufman syndrome) revealed that AVCD, dextrocardia without structural cardiac defects, and abdominal situs inversus were also present. Moreover, clinical evidence from personal series revealed that isolated AVCD or in association with defects that are particularly frequent in the setting of heterotaxy such as common atrium or anomalous pulmonary venous return seem to be an important clinical feature of BBS (Digilio et al., 1999). AVCD have also recently been described in several BBS case reports, the latest of them being the one of Olson and colleagues in 2019who stated that the prevalence of laterality defects such as situs inversus and heterotaxy in patients with BBS is higher than reported in the general population (Olson, Krentz, Finta, Okorie, & Haws, 2019). In the last decade, 19 BBS-related genes (BBS1–BBS19) have been identified, showing critical roles in ciliary morphogenesis and function. Since 1999, clinical observations revealed cardiac anatomical similarities between patients with polydactyly syndromes and heterotaxy and polysplenia with a high prevalence of AVCD (Digilio et al., 1999). Followingmolecular studies on transgenic mice have shown that cilia are required for left-right body axis determination through Shh signaling in secondary heart field and confirmed ciliary dysfunction through Shh signaling impairment in several disorders with polydactyly (Ansley et al., 2003). Indeed, the link between AVCD and BBS is not surprising thanks to anatomical observations andmolecular studies that showed that genes implicated in syndromes with AVCD encode for proteins involved in ciliogenesis (Digilio et al., 2019). Clinical observations and molecular studies therefore support the fact that AVCD in the setting of cardiac laterality defects is to be considered the most important congenital heart disease closely associated to ","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"85 3-4","pages":"101-102"},"PeriodicalIF":1.9,"publicationDate":"2021-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/ahg.12413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38810060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Genotyping complex structural variation at the malaria-associated human glycophorin locus using a PCR-based strategy. 使用基于pcr的策略对疟疾相关人糖蛋白位点复杂结构变异进行基因分型。
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2021-01-01 Epub Date: 2020-09-08 DOI: 10.1111/ahg.12405
Walid Algady, Eleanor Weyell, Daria Mateja, André Garcia, David Courtin, Edward J Hollox
{"title":"Genotyping complex structural variation at the malaria-associated human glycophorin locus using a PCR-based strategy.","authors":"Walid Algady,&nbsp;Eleanor Weyell,&nbsp;Daria Mateja,&nbsp;André Garcia,&nbsp;David Courtin,&nbsp;Edward J Hollox","doi":"10.1111/ahg.12405","DOIUrl":"https://doi.org/10.1111/ahg.12405","url":null,"abstract":"<p><p>Structural variation in the human genome can affect risk of disease. An example is a complex structural variant of the human glycophorin gene cluster, called DUP4, which is associated with a clinically significant level of protection against severe malaria. The human glycophorin gene cluster harbours at least 23 distinct structural variants, and accurate genotyping of this complex structural variation remains a challenge. Here, we use a polymerase chain reaction-based strategy to genotype structural variation at the human glycophorin gene cluster, including the alleles responsible for the U- blood group. We validate our approach, based on a triplex paralogue ratio test, on publically available samples from the 1000 Genomes project. We then genotype 574 individuals from a longitudinal birth cohort (Tori-Bossito cohort) using small amounts of DNA at low cost. Our approach readily identifies known deletions and duplications, and can potentially identify novel variants for further analysis. It will allow exploration of genetic variation at the glycophorin locus, and investigation of its relationship with malaria, in large sample sets at minimal cost, using standard molecular biology equipment.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"85 1","pages":"7-17"},"PeriodicalIF":1.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/ahg.12405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38448662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Detection of mosaicism for segmental and whole chromosome imbalances by targeted sequencing. 利用靶向测序技术检测片段性和全染色体不平衡的嵌合现象。
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2021-01-01 Epub Date: 2020-08-06 DOI: 10.1111/ahg.12402
Darine Villela, Juliana Sobral de Barros, Silvia Souza da Costa, Talita F M Aguiar, Francine Campagnari, Angela M Vianna-Morgante, Ana C V Krepischi, Carla Rosenberg
{"title":"Detection of mosaicism for segmental and whole chromosome imbalances by targeted sequencing.","authors":"Darine Villela,&nbsp;Juliana Sobral de Barros,&nbsp;Silvia Souza da Costa,&nbsp;Talita F M Aguiar,&nbsp;Francine Campagnari,&nbsp;Angela M Vianna-Morgante,&nbsp;Ana C V Krepischi,&nbsp;Carla Rosenberg","doi":"10.1111/ahg.12402","DOIUrl":"https://doi.org/10.1111/ahg.12402","url":null,"abstract":"<p><p>Mosaic segmental and whole chromosome copy number alterations are postzygotic variations known to be associated with several disorders. We have previously presented an efficient targeted sequencing approach to simultaneously detect point mutations and copy number variations (CNVs). In this study, we evaluated the efficiency of this approach to detect mosaic CNVs, using seven postnatal and 19 tumor samples, previously characterized by chromosomal microarray analyses (CMA). These samples harbored a total of 28 genomic imbalances ranging in size from 0.68 to 171 Mb, and present in 10-80% of the cells. All CNV regions covered by the platform were correctly identified in postnatal samples, and only seven out of 19 CNVs from tumor samples were not identified either because of a lack of target probes in the affected genomic regions or an absence of minimum reads for an alteration call. These results demonstrate that, in a research setting, this is a robust approach for detecting mosaicism in cases of segmental and whole chromosome alterations. Although the current sequencing platform presented a resolution similar to genomic microarrays, it is still necessary to further validate this approach in a clinical setting in order to replace CMA and sequencing analyses by a single test.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"85 1","pages":"18-26"},"PeriodicalIF":1.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/ahg.12402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38238404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Mini-review: Role of the PI3K/Akt pathway and tyrosine phosphatases in Alzheimer's disease susceptibility. 迷你综述:PI3K/Akt通路和酪氨酸磷酸酶在阿尔茨海默病易感性中的作用
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2021-01-01 Epub Date: 2020-12-01 DOI: 10.1111/ahg.12410
David Curtis, Sreejan Bandyopadhyay
{"title":"Mini-review: Role of the PI3K/Akt pathway and tyrosine phosphatases in Alzheimer's disease susceptibility.","authors":"David Curtis,&nbsp;Sreejan Bandyopadhyay","doi":"10.1111/ahg.12410","DOIUrl":"https://doi.org/10.1111/ahg.12410","url":null,"abstract":"<p><p>A variety of findings from in vitro experiments and animal models support the hypothesis that one contribution to pathogenesis in Alzheimer's disease (AD) is enhanced phosphorylation of tau protein, which may be triggered by amyloid β (Aβ) and mediated by impaired activity of the PI3K/Akt signaling pathway. A number of tyrosine phosphatases act to reduce PI3K/Akt activity, and inhibition of tyrosine phosphatases is protective against Aβ toxicity in cell cultures and whole animals. Results from analysis of exome sequenced late onset AD cases and controls similarly show that rare coding variants predicted to damage PI3K functioning increase AD risk, whereas those which are predicted to damage genes for tyrosine phosphatase genes are protective. Taken together, these results support the proposition that tyrosine phosphatase antagonists might be trialed as therapeutic agents to protect against the development of AD.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"85 1","pages":"1-6"},"PeriodicalIF":1.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/ahg.12410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38661957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Osteogenesis imperfecta: Novel genetic variants and clinical observations from a clinical exome study of 54 Indian patients. 成骨不全:来自54名印度患者临床外显子组研究的新型遗传变异和临床观察。
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2021-01-01 Epub Date: 2020-08-07 DOI: 10.1111/ahg.12403
Vrisha Madhuri, Agnes Selina, Lakshmi Loganathan, Ashis Kumar, Vignesh Kumar, Renita Raymond, Sowmya Ramesh, Nimmy Vincy, Giftson Joel, Deeptiman James, Madhavi Kandagaddala, Antonisamy B
{"title":"Osteogenesis imperfecta: Novel genetic variants and clinical observations from a clinical exome study of 54 Indian patients.","authors":"Vrisha Madhuri,&nbsp;Agnes Selina,&nbsp;Lakshmi Loganathan,&nbsp;Ashis Kumar,&nbsp;Vignesh Kumar,&nbsp;Renita Raymond,&nbsp;Sowmya Ramesh,&nbsp;Nimmy Vincy,&nbsp;Giftson Joel,&nbsp;Deeptiman James,&nbsp;Madhavi Kandagaddala,&nbsp;Antonisamy B","doi":"10.1111/ahg.12403","DOIUrl":"https://doi.org/10.1111/ahg.12403","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is a group of inherited disorders with increased bone fragility and wide genetic heterogeneity. We report the outcome of clinical exome sequencing validated by Sanger sequencing in clinically diagnosed 54 OI patients in Indian population. In 52 patients, we report 20 new variants involving both dominant and recessive OI-specific genes and correlate these with phenotypes. COL1A1 and COL1A2 gene variants were identified in 44.23%, of which 28.84% were glycine substitution abnormalities. Two novel compound heterozygous variants in the FKBP10 gene were seen in two unrelated probands. A novel heterogeneous duplication of chromosomal region chr17: 48268168-48278884 from exons 1-33 of the COL1A1 gene was found in one proband. In five probands, there were additional variants in association with OI. These were ANO5 in association with CRTAP in two probands of the same family causing gnathodiaphyseal dysplasia, COL5A2 with LEPRE1 causing Ehlers Danlos syndrome, COL11A1 in addition to COL1A1 causing Stickler syndrome, and a previously unreported combination of SLC34A1 gene variant with FKBP10 leading to Fanconi renal tubular syndrome type II. Our findings demonstrate the efficacy of clinical exome sequencing in screening OI patients, classifying its subtypes, and identifying associated disorders in consanguineous populations.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"85 1","pages":"37-46"},"PeriodicalIF":1.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/ahg.12403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38251756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Clinical and exome sequencing findings in seven children with Bardet-Biedl syndrome from Turkey. 土耳其7例Bardet-Biedl综合征患儿的临床和外显子组测序结果。
IF 1.9 4区 生物学
Annals of Human Genetics Pub Date : 2021-01-01 Epub Date: 2020-07-20 DOI: 10.1111/ahg.12401
Evren Gumus, Ebru Tuncez, Ozlem Oz, Merve Saka Guvenc
{"title":"Clinical and exome sequencing findings in seven children with Bardet-Biedl syndrome from Turkey.","authors":"Evren Gumus,&nbsp;Ebru Tuncez,&nbsp;Ozlem Oz,&nbsp;Merve Saka Guvenc","doi":"10.1111/ahg.12401","DOIUrl":"https://doi.org/10.1111/ahg.12401","url":null,"abstract":"<p><strong>Background: </strong>Bardet-Biedl syndrome (BBS) is a very-rare autosomal recessive genetic disorder with severe multisystem manifestations. Genetic testing plays an important role in the early diagnosis of the disease. In this study, while trying to elucidate the genetic etiology of seven individuals with clinical BBS diagnosis from six different families, we also aimed to examine the distribution of BBS variations in this region of Turkey.</p><p><strong>Methods and materials: </strong>Exome sequencing analysis is performed for clinically diagnosed patients with BBS in the present study followed by parental segregation. The unreported and previously described clinical features are presented.</p><p><strong>Results: </strong>Homozygous variants, four of which are unreported, in BBS-related genes (BBS5 [c.682-2A > G], MKKS [c.775del], BBS7 [c.849+1G > T], BBS9 [c.965G > A], BBS10 [c.145C > T], LZTFL1[c.384G > A]) are detected for all the seven individuals included in the study. The most common clinical finding is polydactyly followed by renal anomalies. The clinical features not previously described are correlated to the unreported variant.</p><p><strong>Conclusions: </strong>In this study, exome sequencing findings are discussed and four previously unreported disease-associated variants are described including the fifth BBS-implicated LZTFL1 change and possible genotype-phenotype correlation is described.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"85 1","pages":"27-36"},"PeriodicalIF":1.9,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/ahg.12401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38178489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信