Application of Clinical Genetics最新文献

{"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}

{"title":"Optical Genome Mapping Identifies a Novel Unbalanced Translocation Between Chromosomes 4q and 6q Leading to Feeding Difficulties and Hypotonia in a Neonate: A Case Report.","authors":"Ying Wang, Shaohua Bi, Xiaoqing Shi, Liying Dai","doi":"10.2147/TACG.S465244","DOIUrl":"10.2147/TACG.S465244","url":null,"abstract":"<p><p>Optical Genome Mapping (OGM) technology has garnered growing interest for the identification of chromosomal structural variations (SVs), particularly complex ones that are implicated in genetic diseases in humans. In this study, we performed genetic diagnostics on a neonatal patient who presented with feeding difficulties, hypotonia, and an atrial septal defect. We utilized a combination of trio-whole exome sequencing and OGM for our analysis. The results revealed an unbalanced translocation between maternal chromosomes 4 and 6 in the proband, ogm[GRch38]t(4:6)(q35.2;q25.3), resulting in a 2.8 Mb deletion at the 4q35 terminal and a 10.2 Mb duplication at the 6q25 terminal. In summary, this study highlights how OGM, in conjunction with other genetic approaches, can unveil the genetic etiology of complex clinical syndromes. Neonatal patients often exhibit low specific phenotypes, underlining the significance of SV detection.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141198903","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":"Preimplantation Genetic Diagnosis of Androgen Resistance Syndrome Caused by Mutation on the <i>AR</i> Gene in Vietnam.","authors":"Nguyen Thanh Tung, Trieu Tien Sang, Tran Van Khoa, Nguyen Van Phong, Tran Hoang Phuong","doi":"10.2147/TACG.S457634","DOIUrl":"10.2147/TACG.S457634","url":null,"abstract":"<p><strong>Background: </strong>Androgen resistance syndrome or androgen insensitivity syndrome (AIS - Androgen Insensitivity Syndrome, OMIM 300068) is an X-linked recessive genetic syndrome causing disorders of sexual development in males. This disease is caused by mutations in the AR gene located on the X chromosome, which encodes the protein that structures the androgen receptor, with the role of receiving androgens. Mutation of the AR gene causes complete or partial loss of androgen receptor function, thereby androgen not being obtained and exerting its effect on target organs, resulting in abnormalities of the male reproductive system due to this organ system, differentiating towards feminization under the influence of estrogen. Disease prevention can be achieved by using pre-implantation genetic diagnosis, which enables couples carrying the mutation to have healthy offspring.</p><p><strong>Aim: </strong>To carry out preimplantation genetic diagnosis of androgen resistance syndrome.</p><p><strong>Methods: </strong>Sanger sequencing was used to detect the mutation in the blood samples of the couple, their son, and 01 embryo that were biopsied on the fifth day based on the findings of next-generation sequencing (NGS) of the affected son. We combined Sanger sequencing and linkage analysis using short tandem repeats (STR) to provide diagnostic results.</p><p><strong>Results: </strong>We performed preimplantation genetic diagnosis for AIS on an embryo from a couple who had previously had an affected son. Consequently, one healthy embryo was diagnosed without the variant NM_000044: c.796del (p.Asp266IlefsTer30).</p><p><strong>Conclusion: </strong>We report on a novel variant (NM_000044: c.796del (p.Asp266IlefsTer30)) in the AR gene discovered in Vietnam. The developed protocol was helpful for the preimplantation genetic diagnosis process to help families with the monogenic disease of AIS but wish to have healthy children.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11082556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913363","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":"Familial LCAT Deficiency and Low HDL-C Levels: In silico Characterization of Two Rare LCAT Missense Mutations.","authors":"Sebastian Ciro Acosta, Lorena Díaz-Ordóñez, Juan David Gutierrez-Medina, Yisther Katherine Silva-Cuero, Luis Guillermo Arango-Vélez, Andrés Octavio García-Trujillo, Harry Pachajoa","doi":"10.2147/TACG.S438135","DOIUrl":"https://doi.org/10.2147/TACG.S438135","url":null,"abstract":"<p><p>Mutations in the lecithin-cholesterol acyltransferase (<i>LCAT</i>) gene, which catalyzes the esterification of cholesterol, result in two types of autosomal recessive disorders: Familial <i>LCAT</i> deficiency (FLD) and Fish Eye Disease (FED). While both phenotypes are characterized by corneal opacities and different forms of dyslipidemia, such as low levels of high-density lipoprotein-cholesterol (HDL-C), FLD exhibits more severe clinical manifestations like splenomegaly, anemia, and renal failure. We describe the first clinically and genetically confirmed case of FLD in Colombia which corresponds to a 46-year-old woman with corneal opacity, hypothyroidism, and dyslipidemia, who does not have any manifestations of renal failure, with two pathogenic heterozygous missense variants in the <i>LCAT</i> gene: <i>LCAT</i> (NM_000229.2):c.803G>A (p.Arg268His) and <i>LCAT</i> (NM_000229.2):c.368G>C (p.Arg123Pro). In silico analysis of the mutations predicted the physicochemical properties of the mutated protein, causing instability and potentially decreased <i>LCAT</i> function. These compound mutations highlight the clinical heterogeneity of the phenotypes associated with <i>LCAT</i> gene mutations.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10893891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973903","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}