Application of Clinical Genetics最新文献

{"title":"Comparison of Genetic, Auditory Features, and Systemic Clinical Phenotype in 14 Families with Syndromic Hearing Loss.","authors":"Zhoushu Zheng, Lulu Yan, Lu Ding, Yinghui Zhang, Meihong Wang, Yihui Yang, Junhua Wu, Changshui Chen, Ming Tang, Haibo Li","doi":"10.2147/TACG.S472898","DOIUrl":"https://doi.org/10.2147/TACG.S472898","url":null,"abstract":"<p><strong>Introduction: </strong>Syndromic hearing loss (SHL) is characterized by distinctive clinical phenotypes as well as genetic and phenotypic heterogeneity. More than 400 species of SHL have been described, the majority of which are autosomal dominant.</p><p><strong>Methods: </strong>11 forms of SHL were obtained from 14 unrelated families with probands ranging in age from 5 to 78 months. The results of whole exome sequencing(WES), audiological characteristics, middle and inner ear radiological findings, and additional clinical phenotype characteristics were retrospectively analyzed.</p><p><strong>Results: </strong>Fourteen people with SHL were found. Two of them had Waardenburg syndrome, two had Branchio-Oto-Renal syndrome, two had CHARGE syndrome, and one had Treacher Collins syndrome, Kleefstra syndrome, Muenke syndrome, Osteopathia Striata with Cranial Sclerosis, Ayme-Gripp syndrome, Tatton-Brown-Rahman syndrome, Stickler syndrome, or Stapes Ankylosis with Broad Thumbs and Toes. In this investigation, ten variants were first reported.</p><p><strong>Discussion: </strong>The combination of a neonatal hearing screening and WES can diagnose syndrome-type hearing loss in infancy and childhood, according to our findings, expansion of the gene variant spectrum and phenotype for various age groups of SHL is essential and can provide valuable guidelines for clinical intervention decisions. It is imperative for medical practitioners to conduct diligent and prolonged patient monitoring due to the inherent variability in both the auditory impairment and the comprehensive clinical manifestation of SHL.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"17 ","pages":"171-186"},"PeriodicalIF":2.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population.","authors":"Shuang Lv, Yiming Li, Bojian Sun, Yu Jing, Xing Wang, Zhanqing Gu, Bailiang Wang, Cheng Xiao","doi":"10.2147/TACG.S472418","DOIUrl":"https://doi.org/10.2147/TACG.S472418","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objects: &lt;/strong&gt;Rheumatoid arthritis (RA) is a systemic autoimmune disease with an obscure pathogenesis. This study aims to identify the susceptibility conferred by specific single nucleotide polymorphisms (SNPs), namely rs17548629 within the RIPK1 gene and rs10094579 within the RIPK2 gene, in RA. Additionally, it investigates the associations between inflammatory markers and biochemical parameters at various stages of the disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We analyzed 394 patients with RA and 258 normal controls (NCs), examining SNPs within the RIPK1 (rs17548629) and RIPK2 (rs10094579) genes using polymerase chain reaction (PCR) and sequencing techniques. Profiles of RA patients were evaluated for inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, glucose, uric acid, and creatinine. Additionally, disease-specific indicators included cyclic citrullinated peptide (CCP), rheumatoid factor (RF), antinuclear antibodies (ANA), and anti-keratin antibodies. The Disease Activity Score 28 (DAS28), based on ESR, was used to categorize RA patients into groups of high, moderate, or low disease activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We found a significant association between the RIPK1 rs17548629 genotype and RA in the additive model (&lt;i&gt;p&lt;/i&gt; &lt; 0.001; OR = 3.23), over-dominant model (&lt;i&gt;p&lt;/i&gt; &lt; 0.001; OR = 0.27), and dominant model (&lt;i&gt;p&lt;/i&gt; &lt; 0.001; OR = 3.94). The frequency of the C allele at rs17548629 was significantly higher in NCs than in RA patients (&lt;i&gt;p&lt;/i&gt; &lt; 0.001; OR = 0.322). When compared with normal controls, the RIPK1 rs17548629 genotype demonstrated significant associations with both anti-CCP-positive RA patients (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and anti-CCP-negative RA patients (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Similarly, this genotype was associated with RF-positive RA patients (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Furthermore, the RIPK2 rs10094579 genotype was significantly associated with CRP levels in RA patients with low disease activity in the over-dominant model (&lt;i&gt;p&lt;/i&gt; = 0.029; OR = 0.065, adjusted for age and sex).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The presence of the RIPK1 rs17548629 genotype is associated with RA under additive, co-dominant, and dominant models. The T allele mutation at rs17548629 increases the risk of RA in the Chinese population. The RIPK1 rs17548629 genotype was identified as being associated with RF-positive RA patients, whereas no significant association was observed in RF-negative individuals. These findings suggest that this SNP may modulate the risk of RA in an RF-dependent manner. Furthermore, the RIPK2 rs10094579 genotype correlates with CRP levels in RA patients exhibiting low disease activity. This association underscores the necessity for caution when reducing the dosage of therapy in RA patients with low disease activity who carry the CA genotype at RIPK2 rs10094","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"17 ","pages":"159-169"},"PeriodicalIF":2.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consanguinity and Occurrence of Monogenic Diseases in a Single Tertiary Centre in Riyadh, Saudi Arabia: A 2 Years Cross-Sectional Study.","authors":"Lamia K Alshamlani, Dana S Alsulaim, Raghad S Alabbad, Ahad A Alhoshan, Joud F Alkhoder, Norah S Alsaleh, Mohammed Almannai, Faroug Ababneh, Manal Algattan, Lojain Alsini, Abdulrahman Faiz Alswaid, Wafaa M Eyaid, Fuad Al Mutairi, Muhammad Umair, Majid Alfadhel","doi":"10.2147/TACG.S476350","DOIUrl":"10.2147/TACG.S476350","url":null,"abstract":"<p><strong>Background: </strong>Consanguinity, or the practice of marrying close relatives, is a common cultural tradition in Saudi Arabia, with rates among the highest in the world. This practice has significant implications for the prevalence and distribution of major single genetic defects and chromosomal abnormalities within the Saudi population.</p><p><strong>Methods: </strong>Herein, using the BESTCare electronic medical record system (designed to streamline hospital operations, enhance patient care, and improve the overall efficiency of healthcare services; bestcare.ezcaretech.com) in a single tertiary centre, King Abdullah Specialized Children Hospital (KASCH) in Riyadh, Saudi Arabia, we performed a cross-sectional study for all patients referred to the hospital from the 1st January 2020 until 1st January 2022.</p><p><strong>Results: </strong>The present study, which included 1100 individuals, found a high prevalence of consanguinity (64%) and a significant proportion of third-degree relatives (69%). The mean age of participants was 12.24 years, and the diagnostic rate using advanced molecular genetics techniques was 45%, with whole exome sequencing (WES) being the most common method (43%). The study also noted a significant delay in diagnosis for more than a year in 16% of cases, with a common neurodevelopmental phenotype (18%).</p><p><strong>Conclusion: </strong>In conclusion, we revealed the prevalence of consanguineous marriages in the KASCH hospital in Riyadh, Saudi Arabia. We also highlighted the most frequently referred phenotype. These findings are consistent with previous research on the prevalence and impact of consanguinity on rare genetic disorders.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"17 ","pages":"151-158"},"PeriodicalIF":2.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ser434Phe <i>Androgen Receptor</i> Gene Mutation Does Not Affect Fertility but is Associated with Increased Prolactin.","authors":"Nesreen A Saadeh, Marya Obeidat, Mohammad Shboul","doi":"10.2147/TACG.S466919","DOIUrl":"10.2147/TACG.S466919","url":null,"abstract":"<p><strong>Introduction: </strong>Prolactin is a hormone secreted by the anterior pituitary gland essential for lactation. Non-physiological hyperprolactinemia characterized by serum prolactin levels exceeding 20 ng/mL in men and 25 ng/mL in women, often results from medication use or pituitary gland tumors. In a minority of cases, the cause of hyperprolactinemia remains unknown despite clinical investigations. Familial idiopathic hyperprolactinemia may stem from mutations in genes encoding prolactin (<i>PRL</i>) and its receptor (<i>PRLR</i>).</p><p><strong>Methods: </strong>This study investigated genetic polymorphisms in <i>PRL</i> and <i>PRLR</i> genes using polymerase chain reaction (PCR) and Sanger sequencing in three sisters affected by familial idiopathic hyperprolactinemia. No mutations were found in these genes, prompting whole exome sequencing (WES) of the proband to identify other potentially involved genes.</p><p><strong>Results: </strong>WES revealed a heterozygous missense substitution c.1301C>T (p.Ser434Phe) in the <i>androgen receptor</i> (<i>AR</i>) gene. Next-generation sequencing (NGS) for the <i>AR</i> gene confirmed that the proband and her two affected sisters, along with three asymptomatic sisters, were all heterozygous carriers of the mutation. Their father was hemizygous, while their mother had a normal genotype.</p><p><strong>Conclusion: </strong>The heterozygous missense mutation in the <i>AR</i> gene found in this family with familial idiopathic hyperprolactinemia is not yet explained. Hence, further research is warranted to elucidate the functional implications of this mutation on AR and its role in the pathogenesis of hyperprolactinemia.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"17 ","pages":"143-149"},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Class II Transactivator Gene (<i>CIITA</i>) Variants Associated with Bare Lymphocyte Syndrome II in a Female Sudanese Patient.","authors":"Omaima Abdel Majeed Mohamed Salih, Nahla Hashim Hassan Erwa, Abdelrahman Hamza Abdelmoneim, Hiba Awadelkareem Osman Fadl, Brigitte Glanzmann, Manasik Abdalla Babiker Osman, Monzir Ahmed Hassan Osman, Thuraya Mohamed Elshiekh Gasim, Alamin Mustafa","doi":"10.2147/TACG.S472788","DOIUrl":"https://doi.org/10.2147/TACG.S472788","url":null,"abstract":"<p><strong>Introduction: </strong>Inborn errors of immunity (IEI) are disorders that present a health issue, especially in developing countries where there is a high rate of consanguineous marriages and an increasing rate of diagnosis. One of these disorders is Bare Lymphocyte Syndrome II (BLS II) which is a rare and genetically complex disease that has high morbidity and mortality. The exact genotypic and phenotypic characteristics are still poorly characterized especially in developing countries.</p><p><strong>Case presentation: </strong>Here, we report the first case of BLS II in a seven-month-old Sudanese female with recurrent chest infections, dermatitis, persistent diarrhea, and failure to thrive. The patient's all four sisters and three paternal uncles died in early infancy. Laboratory investigations revealed low CD3+, CD4+, and CD8+ lymphocytes, along with normal CD19+ and CD16+ lymphocytes, and low serum IgM and IgA levels. Genetic analysis revealed two <i>CIITA</i> variants; c.2296C >G p. (Pro766Ala) and c.439+1G >A.</p><p><strong>Conclusion: </strong>Further bioinformatics, immunological and clinical workups supported a pathogenic effect of both mutations affecting the function of CIITA protein, and suggesting a compound heterozygote mutation. The patient was started on prophylactic antibiotics and regular intravenous immunoglobulin replacement therapy. The prognosis of this disease is poor in most of the cases, with only a few reported cases surviving until adulthood.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"17 ","pages":"133-141"},"PeriodicalIF":2.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11430264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Sturge-Weber Syndrome: A Review of Pathophysiology, Genetics, Clinical Features, and Current Management Approache [Corrigendum].","authors":"","doi":"10.2147/TACG.S487419","DOIUrl":"https://doi.org/10.2147/TACG.S487419","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/TACG.S363685.].</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"17 ","pages":"131-132"},"PeriodicalIF":2.6,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11328840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the Accuracy in Provisional Diagnosis of 22q11.2 Deletion and Williams Syndromes by Facial Photos in Thai Population Between De-Identified Facial Program and Clinicians.","authors":"Nop Khongthon, Midi Theeraviwatwong, Khunton Wichajarn, Kitiwan Rojnueangnit","doi":"10.2147/TACG.S458400","DOIUrl":"10.2147/TACG.S458400","url":null,"abstract":"<p><strong>Introduction: </strong>There are more than 6000 genetic syndromes, therefore the recognition of facial patterns may present a challenge for clinicians. The 22q11.2 deletion syndrome (22q11.2 DS) and Williams syndrome (WS) are two different genetic syndromes but share some common phenotypic traits and subtle facial dysmorphisms. Therefore, any tool that would help clinicians recognize genetic syndromes would likely result in a more accurate diagnosis.</p><p><strong>Methods: </strong>The syndrome identification accuracy was compared between 2 different facial analysis algorithms (DeepGestalt and GestaltMatcher) of the Face2Gene (F2G) tool and a group of 9 clinicians with different levels of expertise before and after using F2G for a cohort of 64 Thai participants' frontal facial photos divided into 3 groups of 22q11.2 DS, WS and unaffected controls.</p><p><strong>Results: </strong>The higher accuracy from the DeepGestalt algorithm than from clinicians was demonstrated, especially when comparing between the two syndromes. The accuracy was highest when clinicians use the tool combined with their own decision-making process. The tool's second algorithm, GestaltMatcher revealed clear separation among these three groups of photos.</p><p><strong>Discussion: </strong>The result of F2G outperforming clinicians was not surprising. However, the highest increase in accuracy was with nondysmorphology clinicians using F2G.</p><p><strong>Conclusion: </strong>Face2Gene would be a useful tool to help clinicians in facial recognition of genetic syndromes, before ordering specific tests to confirm the definite diagnosis.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"17 ","pages":"107-115"},"PeriodicalIF":2.6,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Diversity of <i>CYP2C19</i> Polymorphisms in the Thai Population: Implications for Precision Medicine.","authors":"Vorthunju Nakhonsri, Shobana John, Hathaichanok Panumasmontol, Manassanan Jantorn, Pongpipat Chanthot, Nuntachai Hanpramukkun, Supaporn Meelarp, Chonlaphat Sukasem, Sissades Tongsima, Sukhontha Hasatsri, Abhisit Prawang, Thanawat Thaingtamtanha, Natchaya Vanwong, Chalirmporn Atasilp, Monpat Chamnanphon, Pimonpan Jinda, Patompong Satapornpong","doi":"10.2147/TACG.S463965","DOIUrl":"10.2147/TACG.S463965","url":null,"abstract":"<p><strong>Introduction: </strong><i>CYP2C19</i> plays a major role in the metabolism of various drugs. The most common genetic variants were the <i>CYP2C19*2</i> and <i>*3</i> alleles (<i>rs4244285</i> and <i>rs4986893</i>, non-functional variants). In previous studies, we found that genetic polymorphisms in <i>CYP2C19</i> variants influenced the active metabolites of clopidogrel and caused major adverse cardiovascular and cerebrovascular effects. However, the distribution of <i>CYP2C19</i> varies among ethnic groups and according to adverse drug reactions. This study aimed to investigate the frequency of <i>CYP2C19</i> genetic polymorphisms in the Thai population and analyze the differences in the frequency of <i>CYP2C19</i> genetic polymorphisms between Thai and other populations.</p><p><strong>Methods: </strong>This study enrolled 211 unrelated healthy Thai individuals in total. We performed a real-time polymerase chain reaction to genotype <i>CYP2C19*2</i> (681G > A) and <i>CYP2C19*3</i> (636G > A).</p><p><strong>Results: </strong>In the Thai population, the <i>CYP2C19*1</i> allele was the most prevalent at 70.14%, while the <i>CYP2C19*2</i> and <i>*3</i> alleles were found at frequencies of 25.36% and 4.50%, respectively. Conversely, the <i>CYP2C19*3</i> allele was not detected in Caucasian, Hispanic, African, Italian, Macedonian, Tanzanian, or North Indian populations. The phenotypic profile of this gene revealed that the frequency of intermediate metabolizers (IMs) is nearly equal to that of extensive metabolizers (EMs), at 42.65% and 48.82% respectively, with genotypes <i>*1/*2</i> (36.02%) and <i>*1/*3</i> (6.63%). Likewise, poor metabolizers (PMs) with genotypes <i>*2/*2</i> (6.16%), <i>*2/*3</i> (2.37%), and <i>*3/*3</i> (<1%) are more prevalent in our population as well.</p><p><strong>Conclusion: </strong>The distribution of <i>CYP2C19</i> genotype and phenotype influenced by non-functional alleles has potential as a pharmacogenomics biomarker for precision medicine and is dependent on an ethnic-specific genetic variation database.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"17 ","pages":"95-105"},"PeriodicalIF":2.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a Novel Homozygous Mutation in <i>MTMR2</i> Gene Causes Very Rare Charcot-Marie-Tooth Disease Type 4B1.","authors":"Nan Du, Xiaolei Wang, Zhaohui Wang, Hongwei Liu, Hui Liu, Hongfang Duan, Shaozhi Zhao, Santasree Banerjee, Xinwen Zhang","doi":"10.2147/TACG.S448084","DOIUrl":"10.2147/TACG.S448084","url":null,"abstract":"<p><strong>Background: </strong>Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders involving peripheral nervous system. Charcot-Marie-Tooth disease 4B1 (CMT4B1) is a rare subtype of CMT. CMT4B1 is an axonal demyelinating polyneuropathy with an autosomal recessive mode of inheritance. Patients with CMT4B1 usually manifested with dysfunction of the motor and sensory systems which leads to gradual and progressive muscular weakness and atrophy, starting from the peroneal muscles and finally affecting the distal muscles. Germline mutations in <i>MTMR2</i> gene causes CMT4B1.</p><p><strong>Material and methods: </strong>In this study, we investigated a 4-year-old Chinese boy with gradual and progressive weakness and atrophy of both proximal and distal muscles. The proband's parents did not show any abnormalities. Whole-exome sequencing and Sanger sequencing were performed.</p><p><strong>Results: </strong>Whole-exome sequencing identified a novel homozygous nonsense mutation (c.118A>T; p.Lys40*) in exon 2 of <i>MTMR2</i> gene in the proband. This novel mutation leads to the formation of a truncated MTMR2 protein of 39 amino acids instead of the wild- type MTMR2 protein of 643 amino acids. This mutation is predicted to cause the complete loss of the PH-GRAM domain, phosphatase domain, coiled-coil domain, and PDZ-binding motif of the MTMR2 protein. Sanger sequencing revealed that the proband's parents carried the mutation in a heterozygous state. This mutation was absent in 100 healthy control individuals.</p><p><strong>Conclusion: </strong>This study reports the first mutation in <i>MTMR2</i> associated with CMT4B1 in a Chinese population. Our study also showed the importance of whole-exome sequencing in identifying candidate genes and disease-causing variants in patients with CMT4B1.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"17 ","pages":"71-84"},"PeriodicalIF":3.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Chromosomal Microarray Analysis in Genetic Reasons of Miscarriage Tissues.","authors":"Zhen Xu, Na Liu, Lu Gao, Dongyi Yu","doi":"10.2147/TACG.S461674","DOIUrl":"10.2147/TACG.S461674","url":null,"abstract":"<p><strong>Background: </strong>The potential causes of miscarriage are very complex, including genetic, immune, infectious, and endocrine factors. 50%-60% of miscarriages are caused by chromosomal abnormalities. Chromosomal microarray analysis (CMA) is a key tool in this context, capable of detecting not only copy number variations (CNV) but also loss of heterozygosity (LOH). CMA has been used as a tool to investigate the genetic reasons for miscarriage.</p><p><strong>Methods: </strong>In our study, chromosomal microarray analysis (CMA) conducted 1220 miscarriage villous tissues. The results from this technology were used to identify the genetic reasons for miscarriage and evaluated strategies for subsequent pre-pregnancy planning.</p><p><strong>Results: </strong>Here, the abnormality rate of miscarriage was 56.07%(684/1220). The aneuploidy rate accounted for 81.14%(555/684), and was significantly higher in group >35-year-old age. The second most common genetic reason for miscarriage was polyploidy, accounting for 10.09%(69/684). Additionally, we discovered loss of heterozygosity (LOH) in a small percentage of cases, accounting for 2.20%(15/684) reason for miscarriage genetic reasons, due to the advantage of CMA can detect isodisomy (a kind of uniparental disomy). 45 cases (6.58%) with copy number variants, which due to the CMA can detect copy number variations.</p><p><strong>Conclusion: </strong>Our study indicated that miscarriage villous tissues should be performed genetic analysis, seek help from professional genetic counseling.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"17 ","pages":"85-93"},"PeriodicalIF":3.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}