Annals of Human Genetics最新文献

{"title":"Molecular genetic diagnosis of kidney ciliopathies: Lessons from interpreting genomic sequencing data and the requirement for accurate phenotypic data","authors":"Sarah Orr,&nbsp;Eric Olinger,&nbsp;Sotia Iosifidou,&nbsp;Miguel Barroso-Gil,&nbsp;Ruxandra Neatu,&nbsp;Katrina Wood,&nbsp;Ian Wilson,&nbsp;Genomics England Research Consortium,&nbsp;John Andrew Sayer","doi":"10.1111/ahg.12508","DOIUrl":"10.1111/ahg.12508","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p><b>Introduction</b>: Massively parallel sequencing (MPS) techniques have made a major impact on the identification of the genetic basis of inherited kidney diseases such as the ciliopathy autosomal dominant polycystic kidney disease (ADPKD). Great care must be taken when analysing MPS data in isolation from accurate phenotypic information, as this can cause misdiagnosis. <b>Methods</b>: Here, we describe a family trio, recruited to the Genomics England 100,000 Genomes Project, labelled as having cystic kidney disease, who were genetically unsolved following routine data analysis pipelines. We performed a bespoke reanalysis of Whole Genome Sequencing (WGS) data and coupled this with revised phenotypic data and targeted PCR and Sanger sequencing to provide a precise molecular genetic diagnosis. <b>Results</b>: We detected a heterozygous <i>PKD1</i> frameshift variant within the WGS data which segregated with the redefined ADPKD phenotypes. An additional heterozygous exon deletion in <i>ALG8</i> was also found in affected and unaffected individuals, but its precise clinical significance remains unclear. <b>Conclusion</b>: This case illustrates that reanalysis of WGS data in unsolved cases of cystic kidney disease is valuable. Clinical phenotypes must be reassessed as these may have been incorrectly recorded and evolve over time. Undertaking additional studies including genotype-phenotype correlation in wider family members provides useful diagnostic information.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"88 1","pages":"76-85"},"PeriodicalIF":1.9,"publicationDate":"2023-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9284677","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":"The impact of obesity on lung function measurements and respiratory disease: A Mendelian randomization study","authors":"Jiayan Liu,&nbsp;Hanfei Xu,&nbsp;L Adrienne Cupples,&nbsp;George T. O’ Connor,&nbsp;Ching-Ti Liu","doi":"10.1111/ahg.12506","DOIUrl":"10.1111/ahg.12506","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Observational studies have shown that body mass index (BMI) and waist-to-hip ratio (WHR) are both inversely associated with lung function, as assessed by forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). However, observational data are susceptible to confounding and reverse causation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We selected genetic instruments based on their relevant large-scale genome-wide association studies. Summary statistics of lung function and asthma came from the UK Biobank and SpiroMeta Consortium meta-analysis (<i>n</i> = 400,102). After examining pleiotropy and removing outliers, we applied inverse-variance weighting to estimate the causal association of BMI and BMI-adjusted WHR (WHRadjBMI) with FVC, FEV1, FEV1/FVC, and asthma. Sensitivity analyses were performed using weighted median, MR-Egger, and MRlap methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that BMI was inversely associated with FVC (effect estimate, −0.167; 95% confidence interval (CI), −0.203 to −0.130) and FEV1 (effect estimate, −0.111; 95%CI, −0.149 to −0.074). Higher BMI was associated with higher FEV1/FVC (effect estimate, 0.079; 95%CI, 0.049 to 0.110) but was not significantly associated with asthma. WHRadjBMI was inversely associated with FVC (effect estimate, −0.132; 95%CI, −0.180 to −0.084) but has no significant association with FEV1. Higher WHR was associated with higher FEV1/FVC (effect estimate, 0.181; 95%CI, 0.130 to 0.232) and with increased risk of asthma (effect estimate, 0.027; 95%CI, 0.001 to 0.053).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We found significant evidence that increased BMI is suggested to be causally related to decreased FVC and FEV1, and increased BMI-adjusted WHR could lead to lower FVC value and higher risk of asthma. Higher BMI and BMI-adjusted WHR were suggested to be causally associated with higher FEV1/FVC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 4","pages":"174-183"},"PeriodicalIF":1.9,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9759606","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":"Identification of pathogenic deep intronic variant and exonic LINE-1 insertion in a patient with Meckel syndrome","authors":"Sachiko Miyamoto,&nbsp;Kazuyuki Nakamura,&nbsp;Mitsuhiro Kato,&nbsp;Mitsuko Nakashima,&nbsp;Hirotomo Saitsu","doi":"10.1111/ahg.12507","DOIUrl":"10.1111/ahg.12507","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <p>Biallelic <i>CC2D2A</i> variants are associated with a wide range of neurodevelopmental disorders including Meckel syndrome. Here we report a Japanese girl with Meckel syndrome harboring a pathogenic deep intronic variant (NM_001378615.1:c.1149+3569A&gt;G) and an exonic LINE-1 insertion, which was predicted to cause aberrant splicing by SpliceAI and was detected by TEMP2 program, respectively. RNA analysis using urine-derived cells (UDCs) showed retention of 149-bp intronic sequences, leading to frameshift. Immunoblotting showed marked reduction of CC2D2A protein in the patient. Our report demonstrated that utilization of transposon detection tool and functional analysis using UDCs will increase diagnostic yield of genome sequencing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 4","pages":"196-202"},"PeriodicalIF":1.9,"publicationDate":"2023-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048542","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":"Three siblings with variable degrees of neuromuscular involvement and congenital sideroblastic anemia: A peculiar phenotype and a surprise genotypic explanation","authors":"Mai Abd El Salam,&nbsp;Khaled Salama,&nbsp;Yasmeen M. M. Selim,&nbsp;Mariam Saad,&nbsp;Rasha Rady,&nbsp;Salem Alawbathani,&nbsp;Sabine Schroeder,&nbsp;Mohamed A. Elmonem,&nbsp;Nour Elkhateeb","doi":"10.1111/ahg.12505","DOIUrl":"10.1111/ahg.12505","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>Introduction: Congenital sideroblastic anemias (CSAs) are a group of inherited bone-marrow disorders manifesting with erythroid hyperplasia and ineffective erythropoiesis. Methods: We describe a detailed clinical and genetic characterization of three siblings with CSA. Results: Two of them had limb-girdle myopathy and global developmental delay. The two elder siblings performed allogenic hematopoietic stem-cell transplantation 5 and 3 years prior with stabilization of the hematological features. Exome sequencing in the non-transplanted sibling revealed a novel homozygous nonsense variant in <i>SLC25A38</i> gene NM_017875.2:c.559C &gt; T; p.(Arg187*) causing autosomal-recessive sideroblastic anemia type-2, and a second homozygous pathogenic previously reported variant in <i>GMPPB</i> gene NM_013334.3:c.458C &gt; T; p.(Thr153Ile) causing autosomal-recessive muscular dystrophy-dystroglycanopathy type B14. With the established diagnosis, hematopoietic stem cell transplantation is now being scheduled for the youngest sibling, and a trial therapy with acetylcholine esterase inhibitors was started for the two neurologically affected patients with partial clinical improvement. Conclusion: This family emphasizes the importance of whole-exome sequencing for familial cases with complex phenotypes and vague neurological manifestations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 4","pages":"166-173"},"PeriodicalIF":1.9,"publicationDate":"2023-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9675243","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":"A de novo low-frequency mosaic variant of KIF1A causes hereditary spastic paraplegia: A literature review","authors":"Mengyuan Liu,&nbsp;Bing Li,&nbsp;Xiaona Wang,&nbsp;Dongxiao Li,&nbsp;Zhenhua Xie,&nbsp;Yuke Li,&nbsp;Yang Gao,&nbsp;Baiyun Chen,&nbsp;Huichun Zhang,&nbsp;Yanli Wang,&nbsp;Chao Gao","doi":"10.1111/ahg.12503","DOIUrl":"10.1111/ahg.12503","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to investigate the pathogenesis and inheritance pattern of a Chinese Han family with hereditary spastic paraplegia and to retrospectively analyze the characteristics of KIF1A gene variants and related clinical manifestations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>High-throughput whole-exome sequencing was performed on members of a Chinese Han family with a clinical diagnosis of hereditary spastic paraplegia, and the sequencing results were validated by Sanger sequencing. Deep high-throughput sequencing was performed on subjects with suspected mosaic variants. The previously reported pathogenic variant loci of the KIF1A gene with complete data were collected, and the clinical manifestations and characteristics of the pathogenic KIF1A gene variant were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A pathogenic heterozygous variant located in the neck coil of the KIF1A gene (c.1139G&gt;C, p.Arg380Pro) was identified in the proband and four additional members of the family. It was derived from the de novo low-frequency somatic-gonadal mosaicism of the proband's grandmother and had a rate of 10.95%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study helps us to better understand the pathogenic mode and characteristics of mosaic variants, and to understand the location and clinical characteristics of pathogenic variants in KIF1A.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 4","pages":"158-165"},"PeriodicalIF":1.9,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12503","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9672879","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":"The genetic era of childhood cancer: Identification of high-risk patients and germline sequencing approaches","authors":"Oscar Alonso-Luna,&nbsp;Gabriela E Mercado-Celis,&nbsp;Jorge Melendez-Zajgla,&nbsp;Marta Zapata-Tarres,&nbsp;Elvia Mendoza-Caamal","doi":"10.1111/ahg.12502","DOIUrl":"10.1111/ahg.12502","url":null,"abstract":"<p>Childhood cancer is a leading cause of death by disease in children ages 5–14, for which there are no preventive strategies. Due to early-age of diagnosis and short period of exposure to environmental factors, increasing evidence suggests childhood cancer could have strong association with germline alterations in predisposition cancer genes but, their frequency and distribution are largely unknown. Several efforts have been made to develop tools to identify children with increased risk of cancer who may benefit from genetic testing but their validation and application on a large scale is necessary. Research on genetic bases of childhood cancer is ongoing, in which several approaches for the identification of genetic variants related to cancer predisposition have been used. In this paper, we discuss the updated efforts, strategies, molecular mechanisms and clinical implications for germline predisposition gene alterations and the characterization of risk variants in childhood cancer.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 3","pages":"81-90"},"PeriodicalIF":1.9,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9566277","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":"Cover Image, Volume 87, Issue 1–2","authors":"","doi":"10.1111/ahg.12504","DOIUrl":"https://doi.org/10.1111/ahg.12504","url":null,"abstract":"<p><b>Cover Image</b>: The cover image is based on the Original Article <i>Proteome changes in autosomal recessive primary microcephaly</i> by Sami Zaqout et al., https://doi.org/10.1111/ahg.12489.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 1-2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50118106","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":"","authors":"","doi":"10.1111/ahg.12485","DOIUrl":"10.1111/ahg.12485","url":null,"abstract":"<p>Retraction: Liu, H., Wang, T., Chen, X., Jiang, J., Song, N., Li, R., Xin, Y. and Xuan, S. (2020). Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease<i>. Annals of Human Genetics</i>. (https://doi.org/10.1111/ahg.12374).</p><p>The above article, published online on 20 January 2020 in Wiley Online Library (www.wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief Rosemary Ekong, the authors, and John Wiley &amp; Sons Ltd./University College London. The retraction has been agreed because there are inconsistencies in Figures 1 and 5 that render the data difficult to interpret and the original data could not be provided to support the conclusions. The authors asked to retract the manuscript because their confidence in the results has been undermined by these inconsistencies.</p>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 1-2","pages":"80"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117590/pdf/AHG-87-80.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9389046","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 nonsense variant in the ATL3 gene is associated with disturbed pain sensitivity, numbness of distal limbs and muscle weakness","authors":"Sanaz Mohammadi,&nbsp;Hossein Jafari Khamirani,&nbsp;Maryam Baneshi,&nbsp;Neda Kamal,&nbsp;Jamal Manoocheri,&nbsp;Mahsa Saffar,&nbsp;Mehdi Dianatpour,&nbsp;Seyed Mohammad Bagher Tabei,&nbsp;Seyed Alireza Dastgheib","doi":"10.1111/ahg.12501","DOIUrl":"10.1111/ahg.12501","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3>1.1 Introduction</h3>\u0000 \u0000 <p>Hereditary sensory neuropathy (HSN) describes as a heterogeneous group of peripheral neuropathies. HSN type 1 (HSN1) is one subtype characterized by distal sensory impairment that occurs in the form of numbness, tingling, or pain. To date, only two variants in the atlastin GTPase 3 (ATL3) gene have been identified that result in hereditary sensory neuropathy type 1F (HSN1F) with autosomal dominantinheritance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3>1.2 Methods</h3>\u0000 \u0000 <p>We sudied and examined who present with sensory disturbances and muscle weakness in their lower limb. Patients underwent Whole Exome Sequencing and Sanger sequencing was performed in families for validation of detected variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3>1.3 Results</h3>\u0000 \u0000 <p>Here, we identified two Iranian families carrying the novel heterozygous stop variant NM_015459.5: c.16C&gt;T, p.Arg6Ter in <i>ATL3</i> that led to disturbed pain and touch sensitivity. This variant in the ATL3 gene was detected in both families (NM_015459.5: c.16C&gt;T, p.Arg6Ter) by whole-exome sequencing and confirmed by Sanger sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3>1.4 Conclusion</h3>\u0000 \u0000 <p>In this study, the subjects manifested weakness of distal limb muscles and numbness of the lower extremities. In addition, some unusual features, including hearing problems and inability to sit and walk presented in one of the patients. Eventually, we provide a case-based review of the clinical features associated with HSN1F. Hitherto, only 11 patients with HSN1F have been reported. We compared our findings to previously reported cases, suggesting that the clinical features are generally variable in the HSN1F patients.</p>\u0000 </section>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 4","pages":"147-157"},"PeriodicalIF":1.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030893","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":"Development of molecular diagnostic platform for α0-thalassemia 44.6 kb (Chiang Rai, --CR) deletion in individuals with microcytic red blood cells across Thailand","authors":"Pinyaphat Khamphikham,&nbsp;Oravee Hanmanoviriya,&nbsp;Somsakul Pop Wongpalee,&nbsp;Thongperm Munkongdee,&nbsp;Kittiphong Paiboonsukwong,&nbsp;Yupin Jopang,&nbsp;Chaowanee Wangchauy,&nbsp;Charan Sancharernsook,&nbsp;Nathawat Jinorose,&nbsp;Sakorn Pornprasert","doi":"10.1111/ahg.12496","DOIUrl":"https://doi.org/10.1111/ahg.12496","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The α⁰-thalassemia 44.6 kb or Chiang Rai (--^CR) deletion has been reported in northern Thailand and is capable of causing hemoglobin (Hb) H disease and a lethal α-thalassemia genotype, Hb Bart's hydrops fetalis, in this region. However, there are no current data regarding the frequency of --^CR nationwide due to a lack of effective diagnostic assay. Therefore, this study aimed to develop a reliable platform for simultaneous genotyping of --^CR and two common α⁰-thalassemias in Thailand (--^SEA and --^THAI) and investigate the frequency of --^CR across Thailand.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Multiplex gap-PCR assay and five renewable plasmid DNA controls for --^CR, --^SEA, --^THAI, α2-globin (<i>HBA2</i>), and β-actin (<i>ACTB</i>) were newly developed and validated with reference methods. The developed assay was further tested on 1046 unrelated individuals with a reduced mean corpuscular volume (MCV) of less than 75 fl for investigating genotypic and allelic spectrum of --^CR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our developed assay showed 100% concordance with reference methods. The results were valid and reproducible throughout hundreds of reactions. Comparison of the genotypic and allelic spectra revealed that heterozygous --^SEA (--^SEA/αα) and --^SEA alleles were dominant with the frequency of 22.85% (239/1046) and 13.34% (279/2092), respectively. Of these, --^THAI and --^CR were relatively rare in this population and comparable to each other with the allelic frequency of 0.14% (3/2092).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study successfully established a reliable molecular diagnostic platform for genotyping of --^CR, --^SEA, and --^THAI in a single reaction. Additionally, we demonstrated the frequency of --^CR in Thailand for the first time and provided knowledge basis for the planning of severe α-thalassemia prevention and control programs in Thailand, where thalassemia is endemic.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"87 3","pages":"137-145"},"PeriodicalIF":1.9,"publicationDate":"2023-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50124741","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}