Annals of Human Genetics最新文献

{"title":"Using potential variable to study gene–gene and gene–environment interaction effects with genetic model uncertainty","authors":"Xiaonan Hu,&nbsp;Zhen Meng","doi":"10.1111/ahg.12470","DOIUrl":"10.1111/ahg.12470","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>One of the critical issues in genetic association studies is to evaluate the risk of a disease associated with gene–gene or gene–environment interactions. The commonly employed procedures are derived by assigning a particular set of scores to genotypes. However, the underlying genetic models of inheritance are rarely known in practice. Misspecifying a genetic model may result in power loss. By using some potential genetic variables to separate the genotype coding and genetic model parameter, we construct a model-embedded score test (MEST). Our test is free of assumption of gene–environment independence and allows for covariates in the model. An effective sequential optimization algorithm is developed. Extensive simulations show the proposed MEST is robust and powerful in most of scenarios. Finally, we apply the proposed method to rheumatoid arthritis data from the Genetic Analysis Workshop 16 to further investigate the potential interaction effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62795854","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}

{"title":"DRD4 polymorphism associated with greater positive affect in response to negative and neutral social stimuli","authors":"T. Lee Gilman,&nbsp;Matthew T. Ford,&nbsp;Aaron M. Jasnow,&nbsp;Karin G. Coifman","doi":"10.1111/ahg.12471","DOIUrl":"10.1111/ahg.12471","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Despite the robustness of <i>DRD4</i> polymorphism associations with brain-based behavioral characteristics in candidate gene research, investigations have minimally explored associations between these polymorphisms and emotional responses. In particular, the prevalent single nucleotide polymorphism (SNP) -521C/T (rs1800955) in the promoter region of <i>DRD4</i> remains unexplored relative to emotions. Here, two independent samples were evaluated using different emotion elicitation tasks involving social stimuli: Study 1 (<i>N</i> = 120) evoked positive and negative emotional responses to validated film clips; Study 2 (<i>N</i> = 122) utilized Cyberball to simulate social rejection and acceptance. Across studies, C/C individuals self-reported higher mean positive affect scores using Likert scales versus T carrier individuals, selectively when presented with neutral or negative (but not positive) social stimuli. The consistent findings across these two studies supports a functional consequence of this <i>DRD4</i> SNP on emotion processing during changing social contexts. Continued investigation will help clarify if a C/C genotype enhances positive emotions under negative circumstances, or if the presence of the T allele reduces positive emotions, and how rs1800955 behavioral associations might generalize across different demographics. Future studies could also reveal if this SNP interacts with other changing environmental conditions to affect emotional responses, such as social limitations during the COVID-19 pandemic.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48881349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel leaky splice variant in centromere protein J (CENPJ)-associated Seckel syndrome","authors":"Navneesh Yadav,&nbsp;Laxmi Kirola,&nbsp;Thenral S Geetha,&nbsp;Kirti Mittal,&nbsp;Jayarama Kadandale,&nbsp;Yuval Yogev,&nbsp;Ohad S. Birk,&nbsp;Neerja Gupta,&nbsp;Prahlad Balakrishnan,&nbsp;Manisha Jana,&nbsp;Meena Gupta,&nbsp;Madhulika Kabra,&nbsp;Bittianda Kuttapa Thelma","doi":"10.1111/ahg.12469","DOIUrl":"10.1111/ahg.12469","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Primary microcephaly and Seckel syndrome are rare genetically and clinically heterogenous brain development disorders. Several exonic/splicing mutations are reported for these disorders to date, but ∼40% of all cases remain unexplained. We aimed to uncover the genetic correlate(s) in a family of multiple siblings with microcephaly. A novel homozygous intronic variant (NC_000013.10:g.25459823T&gt;C) in <i>CENPJ</i> (13q12) segregating with all four affected male siblings was identified by exome sequencing and validated by targeted linkage approach (logarithm of the odds score 1.8 at θ 0.0). RT-PCR of <i>CENPJ</i> in affected siblings using their EBV derived cell lines showed aberrant transcripts suggestive of exon skipping confirmed by Sanger sequencing. Significantly reduced wild type transcript/protein in the affected siblings having the splice variant indicates a leaky gene expression of pathological relevance. Based on known <i>CENPJ</i> function, assessing for mitotic alterations revealed defect in centrosome duplication causing mono/multicentrosome(s) at prophase, delayed metaphase, and unequal chromosomal segregation in patient cells. Clinical features witnessed in this study expand the spectrum of <i>CENPJ</i>-associated primary microcephaly and Seckel syndrome. Furthermore, besides the importance of regulatory variants in classical monogenic disorders these findings provide new insights into splice site biology with possible implications for ASO-based therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47623842","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}

{"title":"No significant association between SNPs in the CLOCK and ADH4 genes and susceptibility to cluster headaches: A systematic review and meta-analysis","authors":"Jiarui Cui,&nbsp;Wei Peng,&nbsp;Ting Yi,&nbsp;Ping Gao,&nbsp;Mingze Zhou,&nbsp;Tianmin Zhu","doi":"10.1111/ahg.12467","DOIUrl":"10.1111/ahg.12467","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The circadian locomotor output cycles kaput (<i>CLOCK</i>) gene and the alcohol dehydrogenase 4 (<i>ADH4</i>) gene are promising candidates for susceptibility to cluster headaches (CH). Associations of the three single nucleotide polymorphisms (SNPs)—<i>CLOCK</i> SNP rs1801260 and <i>ADH4</i> SNPs rs1800759, and rs1126671—with CH were studied previously, but the results were inconsistent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Associations between the three SNPs (rs1801260, rs1126671, and rs1800759) and CH risk were separately assessed by pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) based on five different genetic models. Methodological quality was assessed using the Newcastle–Ottawa Quality Assessment Scale (NOS). All statistical analyses were carried out with RevMan 5.3 software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight studies involving 1437 CH patients and 2541 healthy controls were selected for quantitative synthesis, from five studies on <i>CLOCK</i> rs1801260, five on <i>ADH4</i> rs1800759, and three on <i>ADH4</i> rs1126671. Our pooled data did not support associations between the three SNPs (rs1801260 in the <i>CLOCK</i> gene, rs1800759 and rs1126671 in the <i>ADH4</i> gene) and susceptibility to CH (rs1801260: OR 1.10, 95% CI: 0.95–1.28; <i>p</i> = 0.19; rs1800759: OR 1.06, 95% CI: 0.93–1.22; <i>p</i> = 0.37; and rs1126671: OR 1.09, 95% CI: 0.92–1.28; <i>p</i> = 0.32).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We found no significant associations between the three SNPs (rs1801260 in the <i>CLOCK</i> gene and rs1800759 and rs1126671 in the <i>ADH4</i> gene) and the susceptibility to CH across both Caucasian and Asian ethnicities in our meta-analysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46264665","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}

{"title":"Association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and H-type hypertension: A systematic review and meta-analysis","authors":"Shengyu Liao,&nbsp;Shuxia Guo,&nbsp;Rulin Ma,&nbsp;Jia He,&nbsp;Yizhong Yan,&nbsp;Xianghui Zhang,&nbsp;Xinping Wang,&nbsp;Boyu Cao,&nbsp;Heng Guo","doi":"10.1111/ahg.12468","DOIUrl":"10.1111/ahg.12468","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The polymorphism of methylenetetrahydrofolate reductase (<i>MTHFR</i>) gene <i>C677T</i> has been linked to H-type hypertension. But the conclusion remained controversial. To elucidate this issue, we performed a comprehensive meta-analysis to analyze the <i>MTHFR C677T</i> polymorphism and H-type hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>The English and Chinese databases were systematically searched to identify relevant studies until November 2020. RevMan 5.3 and Stata 12.0 software were used for meta-analysis. The odds ratio (ORs) and 95% confidence intervals (95% CIs) were used to assess the relationship between the <i>MTHFR C677T</i> polymorphism and H-type hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 14 studies involving 1769 cases and 1443 controls were included. The meta-analysis results showed the association between <i>MTHFR C677T</i> polymorphism and H-type hypertension with the homozygous codominant model (OR = 3.30, 95% CI = 1.94–5.60), heterozygous codominant model (OR = 2.34, 95% CI = 1.53–3.58), dominant model (OR = 1.79, 95% CI = 1.33–2.41), recessive model (OR = 2.70, 95% CI = 1.73–4.21),and the allelic model (OR = 1.82, 95% CI = 1.41–2.35). All <i>p</i>-values were less than 0.05. Therefore, <i>MTHFR C677T</i> polymorphism has a positive correlation with the risk of H-type hypertension. Among them, TT mutation has the greatest impact on the activity of this enzyme, which causes Hcy to rise and leads to H-type hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, our results provide sufficient data to support the hypothesis that the <i>MTHFR C677T</i> polymorphism is related to H-type hypertension susceptibility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42753093","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}

{"title":"Genetic and environmental correlational structure among metabolic syndrome endophenotypes","authors":"Stacey S. Cherny,&nbsp;Frances M. K. Williams,&nbsp;Gregory Livshits","doi":"10.1111/ahg.12465","DOIUrl":"10.1111/ahg.12465","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Metabolic syndrome (MetS) is diagnosed by the presence of high scores on three or more metabolic traits, including systolic and diastolic blood pressure (SBP, DBP), glucose and insulin levels, cholesterol and triglyceride (TG) levels, and central obesity. A diagnosis of MetS is associated with increased risk of cardiovascular disease and type 2 diabetes. The components of MetS have long been demonstrated to have substantial genetic components, but their genetic overlap is less well understood. The present paper takes a multi-prong approach to examining the extent of this genetic overlap. This includes the quantitative genetic and additive Bayesian network modeling of the large TwinsUK project and examination of the results of genome-wide association study (GWAS) of UK Biobank data through use of LD score regression and examination of the number of genes and pathways identified in the GWASes which overlap across MetS traits. Results demonstrate a modest genetic overlap, and the genetic correlations obtained from TwinsUK and UK Biobank are nearly identical. However, these correlations imply more genetic dissimilarity than similarity. Furthermore, examination of the extent of overlap in significant GWAS hits, both at the gene and pathway level, again demonstrates only modest but significant genetic overlap. This lends support to the idea that in clinical treatment of MetS, treating each of the components individually may be an important way to address MetS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913712","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}

{"title":"Deleted genes associated with obesity in Mexican patients diagnosed with nonalcoholic fatty liver disease","authors":"José Francisco Zambrano-Zaragoza,&nbsp;Alejandro Vázquez-Reyes,&nbsp;Ma. de Jesús Durán-Avelar,&nbsp;Jorge Gutiérrez-Franco,&nbsp;Norberto Vibanco-Pérez,&nbsp;Juan Manuel Agraz-Cibrián,&nbsp;Horacio Pérez-Cambero,&nbsp;Miriam Fabiola Ayón-Pérez","doi":"10.1111/ahg.12466","DOIUrl":"10.1111/ahg.12466","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic condition in which both lifestyle and genetic factors have a pathogenic role. The <i>LEP</i> gene encodes leptin, which regulates appetite, body weight, and several metabolic functions. Proopiomelanocortin (POMC), regulates food intake and energy balance. The aim of the study was to determine partial or complete deletions of genes associated with obesity in patients diagnosed with NAFLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and methods</h3>\u0000 \u0000 <p>Blood samples and DNA from 43 individuals diagnosed with NAFLD by ultrasonographic technique (Fibroscan) were obtained. The partial or complete deletions of genes were determined by MLPA (Multiplex Ligation-dependent Probe Amplification) using the SALSA probemix P220-B2 Obesity only on 43 individuals. Fifty blood samples from healthy individuals were included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eleven out of 43 individuals analyzed by MLPA presented some deletion of the genes analyzed: six were female and five were male. The partial or complete deletion of the <i>LEPR</i> and <i>POMC</i> genes was observed in eight patients (18.6%), <i>SIM1</i> in six patients (13.9%), <i>GRIK2</i> and <i>SH2B1</i> in two patients (4.7%), <i>SEZGL2</i> in four patients (9.3%), and <i>MCR4</i> in one patient (2.3%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Partial deletion was observed in <i>LEPR, POMC, SIM1, GRIK2, SH2B1, SEZGL2</i>, and <i>MCR4</i> genes in 26% of the cases, and we suggest that these alterations probably has a potential relationship for the development of NAFLD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2022-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48056103","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}

{"title":"Whole genome sequencing identifies rare genetic variants in familial pancreatic cancer patients","authors":"Ming Tan,&nbsp;Klaus Brusgaard,&nbsp;Anne-Marie Gerdes,&nbsp;Martin Jakob Larsen,&nbsp;Michael Bau Mortensen,&nbsp;Sönke Detlefsen,&nbsp;Ove B. Schaffalitzky de Muckadell,&nbsp;Maiken Thyregod Joergensen","doi":"10.1111/ahg.12464","DOIUrl":"10.1111/ahg.12464","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and fatal malignancies worldwide with an estimated 5-year survival of just 5% (Naghavi et al., <span>2019</span>; McGuigan et al., <span>2018</span>). Familial pancreatic cancer (FPC) is defined as having two or more first-degree relatives (FDRs) with PDAC without known inherited cancer syndrome, and is responsible for up to 10% of all cases of PDAC (Diaz &amp; Lucas, <span>2019</span>). Families fulfilling the FPC criteria represent up to 80% of all families with PDAC aggregation (Llach et al., <span>2020</span>). We have recently estimated the heritability of FPC as high as 0.51 (Tan et al., <span>2021a</span>). The estimated relatively high genetic contribution to FPC calls for efforts to find the genetic variants underlying the genetic predisposition to FPC. Studies using next-generation sequencing (NGS) technique have detected rare sequence variations in <i>BRCA1</i>, <i>BRCA2</i>, <i>CDKN2A</i>, <i>PALB2</i>, and <i>ATM</i> genes to be related to FPC (Roberts et al., <span>2016</span>; Zhen et al., <span>2015</span>). However, those variants are only observed in about 12% of all FPC cases. The suspected germline contribution to over 80% of all FPC cases still remains unknown (Chaffee et al., <span>2018</span>).</p><p>Whole genome sequencing (WGS) can be used to explore genomic alterations in cancer and help us to better understand the whole landscape of mutational signatures in the cancer genomes and to elucidate their functional or clinical implications (Nakagawa &amp; Fujita, <span>2018</span>). Using WGS analysis, Roberts et al. (<span>2016</span>) demonstrated that the genetic architecture of FPC is highly heterogeneous. Genetic heterogeneity refers to: (1) allelic heterogeneity, where different variants at a single gene locus cause the same or similar phenotypic expressions of a disease and (2) locus heterogeneity, where variants at different gene loci cause the same or similar phenotypes of a disease (McClellan &amp; King, <span>2010</span>). The genetic heterogeneity of FPC means that susceptibility variants could be private to certain individuals or families. The situation renders the traditional association analysis for common variants underpowered. Both allelic and locus heterogeneity impose challenges in identifying the relevant genetic variants for FPC. More high-coverage sequencing analyses are required to uncover the genetic diversity in FPC.</p><p>We have performed a WGS on PDAC patients from 27 FPC predisposed families from a recently established national cohort—with a focus on detecting rare genetic variants for the disease. We report findings from the WGS study and compare with published results from previous studies to validate and verify the detected genetic alterations as potential hotspots of functional variations for FPC.</p><p>In total, benign FFPE nonpancreatic tissue samples were available from 35 FPC patients (14 males, 21 females) for DNA ex","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/66/AHG-86-195.PMC9313800.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40310957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel missense variant in CEACAM16 gene causes autosomal dominant nonsyndromic hearing loss","authors":"Dejun Zhang,&nbsp;Jie Wu,&nbsp;Yongyi Yuan,&nbsp;Xiaohong Li,&nbsp;Xue Gao,&nbsp;Mingyu Han,&nbsp;Song Gao,&nbsp;Shasha Huang,&nbsp;Pu Dai","doi":"10.1111/ahg.12463","DOIUrl":"10.1111/ahg.12463","url":null,"abstract":"<p>Hearing loss is the most common sensorineural disorder in humans. It is estimated that more than half of cases of hearing loss are attributable to hereditary causes. Autosomal dominant nonsyndromic hearing loss (ADNSHL) is a paradigm of genetic heterogeneity with more than 45 causative genes identified to date (http://hereditaryhearingloss.org/). These genes play an essential role in the morphology and development of hair cells, synaptic transmission of the auditory nerve, and other roles in the inner ear. For example, the transmembrane channel-like gene1 (<i>TMC1</i>) is specifically required for hair cell mechanoelectrical transduction and is a functionally redundant stereocilia component (Kawashima et al., <span>2011</span>; Pan et al., <span>2013</span>) and eyes absent 4 (<i>EYA4</i>), a member of the vertebrate EYA gene family of transcriptional activators, is important for the development and maturation of the organ of Corti (Wayne et al., <span>2001</span>). However, many genes causing deafness remain unidentified (Ding et al., <span>2020</span>; Fu et al., <span>2021</span>; Qian et al., <span>2020</span>; Zhang et al., <span>2021</span>; Zhu et al., <span>2018</span>). It is therefore important to identify these genes and their functions in the inner ear.</p><p>Carcinoembryonic antigen-related cell adhesion molecule 16 (<i>CEACAM16</i>, MIM 614591) is a member of the CEACAM family, which is known to play a role in tissue architecture and homeostasis, cell growth and differentiation, angiogenesis, and tumor suppression (Kuespert et al., <span>2006</span>). <i>CEACAM16</i> maps to the DFNA4B locus on chromosome 19q13.32 and encodes a protein of 425 amino acids. Although the specific functions of the protein encoded by <i>CEACAM16</i> are still not clear, available evidence indicates that <i>CEACAM16</i> is crucial for hearing maintenance as a structural component of the tectorial membrane (Kammerer et al., <span>2012</span>). <i>CAMCAM16</i> mutations can lead to late-onset bilateral progressive sensorineural hearing loss that begin in the first or second decade (Wang et al.,2015). To date, three <i>CEACAM16</i> missense variants associated with ADNSHL have been reported (Hofrichter et al., <span>2015</span>; Wang et al., <span>2015</span>; Zheng et al., <span>2011</span>). Additionally, Booth et al. (<span>2018</span>) and Dias et al. (<span>2019</span>) described loss of function variants in <i>CEACAM16</i> that can cause autosomal recessive nonsyndromic hearing loss (ARNSHL).</p><p>In this study, we identified a novel missense variant in the <i>CEACAM16</i> gene, c.763A&gt;G; (p.Arg255Gly) in a Chinese family using targeted next-generation sequencing approach. The phenotype was consistent with ADNSHL. Further functional experiments were carried out to evaluate the pathogenesis resulting from this mutation.</p><p>The tectorial membrane is essential for normal hearing due to its exclusive physical properties and its role in modulating","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41099460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ursula Mittwoch: Pioneering geneticist who solved the riddle of sexes","authors":"Nick Lane","doi":"10.1111/ahg.12461","DOIUrl":"10.1111/ahg.12461","url":null,"abstract":"","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2022-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42209511","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}