The Application of Clinical Genetics最新文献

{"title":"Long Non-Coding RNAs ASB16-AS1 and AFAP1-AS1: Diagnostic, Prognostic Impact and Survival Analysis in Colorectal Cancer.","authors":"Naglaa S Elabd,&nbsp;Shimaa E Soliman,&nbsp;Moamena S Elhamouly,&nbsp;Suzy F Gohar,&nbsp;Ayman Elgamal,&nbsp;Mahmoud Magdy Alabassy,&nbsp;Haitham A Soliman,&nbsp;Abdelnaser A Gadallah,&nbsp;Osama D Elbahr,&nbsp;Ghada Soliman,&nbsp;Amany A Saleh","doi":"10.2147/TACG.S370242","DOIUrl":"https://doi.org/10.2147/TACG.S370242","url":null,"abstract":"<p><strong>Background: </strong>We aimed to evaluate the diagnostic roles of AFAP1-AS1 and ASB16-AS1 in colorectal cancer and highlight their roles in predicting colorectal cancer patients' prognosis.</p><p><strong>Methods: </strong>In this case-control study, 146 participants were involved. Group I included 47 patients with CRC. Group II composed of 49 patients with benign lesions in the colon, and Group III included 50 apparently normal subjects of coincided age and gender as controls. All participants were subjected to clinical and endoscopic evaluations, CA19-9, CEA, and quantification of relative expression of lncRNAs ASB16-AS1 and AFAP1-AS1.</p><p><strong>Results: </strong>CRC patients had significantly elevated expression levels of both lncRNAs in tissue and plasma samples versus benign and control groups (p < 0.001). Despite the higher sensitivity of tissue samples results, the relative expression of both lncRNAs in plasma samples was very encouraging in the discrimination between patients with CRC versus control and benign groups. Furthermore, both lncRNAs could discriminate patients with early-stage CRC (stage I&II) from being colonic lesion and control groups with better sensitivity and specificity presented by ASB16-AS1 in tissue and plasma than results detailed by AFAP1-AS1. High expression levels of ASB16-AS1 in tissue and plasma and tissue lncRNA AFAP1-AS1 are significantly correlated with decreased overall survival (p < 0.001) and reduced progression-free (p < 0.001) compared to low expression in CRC patients.</p><p><strong>Conclusion: </strong>We propose the utilization of lncRNA ASB16-AS1 and lncRNA AFAP1-AS1 as biomarkers in diagnosis and prognosis estimation for CRC patients. Moreover, their value in early CRC patients may affect the assortment of target therapy and treatment protocols.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" ","pages":"97-109"},"PeriodicalIF":3.1,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/97/08/tacg-15-97.PMC9355339.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40593022","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":"Utility of Measuring Fetal Cavum Septum Pellucidum (CSP) Width During Routine Obstetrical Ultrasound for Improving Diagnosis of 22q11.2 Deletion Syndrome: A Case-Control Study.","authors":"Christy L Pylypjuk,&nbsp;Shiza F Memon,&nbsp;Bernard N Chodirker","doi":"10.2147/TACG.S364543","DOIUrl":"https://doi.org/10.2147/TACG.S364543","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the utility of measuring fetal cavum septum pellucidum (CSP) width during routine, mid-pregnancy ultrasound for improving diagnosis of 22q11.2 deletion syndrome amongst fetuses with and without conotruncal anomalies.</p><p><strong>Patients and methods: </strong>This was a retrospective case-control study (2005-2016). Fetuses and newborns with 22q11.2 deletion and/or conotruncal cardiac anomalies were identified using a regional, clinical database. A control group was assembled in a 2:1 ratio to create three groups for comparison: i) 22q11.2 deletion syndrome; ii) isolated conotruncal anomalies; and iii) controls. Eligibility was restricted to those with stored ultrasound images between 18-22 weeks' gestation and a minimum biparietal diameter of 40 mm. Post-processing measurement of CSP width was performed in a standardized fashion by two blinded and independent study personnel. Descriptive and inferential statistics, regression modeling, and receiver operator curves (ROC) were used to compare outcomes between groups and evaluate sensitivity/specificity of CSP width as a marker of 22q11.2 deletion syndrome.</p><p><strong>Results: </strong>Twenty-nine cases of 22q11.2 deletion and 64 cases of isolated conotruncal anomalies were matched to 186 healthy controls. Cases with 22q11.2 deletion syndrome had significantly larger CSP widths (5.36 mm; SD=1.2) compared to those with isolated conotruncal anomalies (3.75 mm; SD=1.11) and healthy controls (2.93 mm; SD=0.57; <i>p</i><0.0001). There was no difference in CSP width amongst those with 22q11.2 deletion irrespective of the presence/absence of a conotruncal anomaly (<i>p</i>=0.362), or by type of conotruncal anomaly (<i>p</i>=0.211). Using a CSP width cutoff >4.3 mm, fetuses with 22q11.2 deletion can be accurately identified with good sensitivity (89.7%) and specificity (84%).</p><p><strong>Conclusion: </strong>Fetuses with 22q11.2 deletion syndrome have dilated CSPs when compared to those with isolated conotruncal anomalies or controls. Because CSP dilation can be evaluated during routine mid-pregnancy ultrasound using standard images of the fetal head, measurement could easily be incorporated to enhance prenatal diagnosis of this phenotypically diverse condition.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" ","pages":"87-95"},"PeriodicalIF":3.1,"publicationDate":"2022-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/90/b2/tacg-15-87.PMC9341354.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40580096","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":"Deregulation of CircANXA2, Circ0075001, and CircFBXW7 Gene Expressions and Their Predictive Value in Egyptian Acute Myeloid Leukemia Patients.","authors":"Safaa I Tayel,&nbsp;Shimaa E Soliman,&nbsp;Iman A Ahmedy,&nbsp;Mohamed Abdelhafez,&nbsp;Aly M Elkholy,&nbsp;Amira Hegazy,&nbsp;Nashwa M Muharram","doi":"10.2147/TACG.S365613","DOIUrl":"https://doi.org/10.2147/TACG.S365613","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is of heterogeneous pathogenesis and caused by alterations of multiple genes. CircRNAs act as oncogenes or tumor suppressors in numerous tumors and could be novel diagnostic and prognostic biomarkers. Few studies had incorporated circRNAs in AML.</p><p><strong>Aim of the work: </strong>Assessment of circANXA2, circ0075001, and circFBXW7 gene expressions in AML patients. Evaluation of their relations with clinical, cytogenetic, and overall survival outcome to emphasize their diagnostic role and prognostic impact.</p><p><strong>Methods: </strong>This study was carried out on 120 subjects (66 AML patients and 54 controls). All subjects were subjected to gene expressions assay for circANXA2, circ0075001, circFBXW7 by quantitative real-time polymerase chain reaction.</p><p><strong>Results: </strong>Prominent overexpression of circANAX2 and circ0075001 in patients than control (P < 0.001), whereas circFBXW7 was markedly downregulated in patients than in control (P < 0.001). Moreover, circANXA2 with AUC 0.824, P <0.001, had a sensitivity of 74.24%, specificity 88.89% whereas circ0075001 with AUC 0.855, P < 0.001, had the highest sensitivity of 83.33% and specificity 79.63%, and circFBXW7 with AUC 0.826, P < 0.001, had a sensitivity of 75.76% and specificity 74.07% in the distinction of AML patients from controls. Additionally, we find out that high expression of circANXA2 and circ0075001 correlated significantly with splenomegaly, hepatomegaly, less differentiated FAB subtypes (M5, M7), short overall survival, and had an adverse cytogenetic pattern.</p><p><strong>Conclusion: </strong>CircANXA2, circ0075001, and circFBXW7 gene expressions could serve as potential diagnostic biomarkers for AML disease. Moreover, CircANXA2 and circ0075001 exert poor prognostic effects on AML patients.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" ","pages":"69-85"},"PeriodicalIF":3.1,"publicationDate":"2022-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/31/70/tacg-15-69.PMC9300747.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40535574","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":"A Novel <i>POGZ</i> Variant in a Patient with Intellectual Disability and Obesity.","authors":"Sebastian Giraldo-Ocampo,&nbsp;Rafael Adrian Pacheco-Orozco,&nbsp;Harry Pachajoa","doi":"10.2147/TACG.S369483","DOIUrl":"https://doi.org/10.2147/TACG.S369483","url":null,"abstract":"<p><p>White-Sutton syndrome is a rare type of autosomal dominant neurodevelopmental disorder caused by mutations, mostly <i>de novo</i>, in the <i>POGZ</i> gene. No more than 120 patients have been described so far in the literature. Common clinical manifestations include intellectual disability, developmental delay, autism spectrum disorder, other behavioral abnormalities, sleeping problems, hyperactivity and visual problems. We describe a 20-year-old male patient from Colombia who presented with delayed psychomotor development, intellectual disability, obesity, sleep difficulties, hypotonia, hypogonadism, gynecomastia, visual abnormalities and several facial dysmorphisms. Genetic testing showed a novel heterozygous frameshift variant (c.3308del; p.Leu1103Profs*19) in the <i>POGZ</i> gene (NM_015100.3). This is the first report of a diagnosed patient with WHSUS in Colombia.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" ","pages":"63-68"},"PeriodicalIF":3.1,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f4/b3/tacg-15-63.PMC9271277.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40497742","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":"Novel Compound Heterozygous Variants in the <i>CDC6</i> Gene in a Russian Patient with Meier-Gorlin Syndrome.","authors":"Viktoriia Zabnenkova,&nbsp;Olga Shchagina,&nbsp;Olga Makienko,&nbsp;Galina Matyushchenko,&nbsp;Oxana Ryzhkova","doi":"10.2147/TACG.S342804","DOIUrl":"https://doi.org/10.2147/TACG.S342804","url":null,"abstract":"Background Meier-Gorlin syndrome (MGS) is a rare genetic syndrome inherited in an autosomal dominant or autosomal recessive manner. The disorder is characterized by bilateral microtia, absence or hypoplasia of the patella, and an intrauterine growth retardation as well as a number of other characteristic features. The cause of the disease is mutations in genes encoding proteins involved in the regulation of the cell cycle (ORC1, ORC4, ORC6, CDT1, CDC6, GMNN, CDC45L, MCM3, MCM5, MCM7, GINS2, and DONSON). Meier-Gorlin syndrome 5 due to mutations in the CDC6 gene is difficult to diagnose, and few clinical data have been described to date. Only one patient (male) with a missense mutation in a homozygous state has been previously reported. This report describes a new clinical case of Meier-Gorlin syndrome 5. This is also the first report of a Russian patient with Meier-Gorlin syndrome. Case Presentation The patient, a female, had extremely low physical development, neonatal progeroid appearance, lipodystrophy, thin skin, partial alopecia, cyanosis of the face, triangular face, microgenia, arachnodactyly, delayed bone age, hepatomegaly, hypoplasia of the labia majora, and hypertrophy of the clitoris in addition to known clinical signs. Differential diagnosis was performed with chromosomal abnormalities and Hutchinson-Gilford progeria. According to the results of sequencing of the clinical exome, the patient had two previously undescribed variants in the CDC6 gene, c.230A>G (p.(Lys77Arg)) and c.232C>T (p.(Gln78Ter)), NM_001254.3, in a compound heterozygous state. Conclusion This case allows us to learn more about the clinical features and nature of MGS 5 and improve the speed of diagnostics and quality of genetic counseling for such families.","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":" ","pages":"1-10"},"PeriodicalIF":3.1,"publicationDate":"2022-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/6a/tacg-15-1.PMC8747802.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816513","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":"First Two Case Reports of Becker's Type Myotonia Congenita in Colombia: Clinical and Genetic Features.","authors":"Jorge Andres Olave-Rodriguez,&nbsp;Francisco Javier Bonilla-Escobar,&nbsp;Estephania Candelo,&nbsp;Lisa Ximena Rodriguez-Rojas","doi":"10.2147/TACG.S323559","DOIUrl":"https://doi.org/10.2147/TACG.S323559","url":null,"abstract":"<p><strong>Background: </strong>Becker's type myotonia congenita is an autosomal recessive nondystrophic skeletal muscle disorder characterized by muscle stiffness and the inability of muscle relaxation after voluntary contraction. It is caused by mutations in the <i>CLCN1</i> gene, which encodes for a chloride channel mainly expressed in the striated muscle. Most cases have been reported in the European population, and only mexiletine has demonstrated a randomized placebo-controlled, double-blinded effectiveness.</p><p><strong>Case presentation: </strong>We present two male siblings from Colombia with Latino ancestry, without parental consanguinity, with myotonia during voluntary movements, muscle hypertrophy of lower extremities, transient weakness, and severe muscle fatigue after exercise from three years of age. A genetic panel for dystrophic muscle disorders and a muscle biopsy were both negative. Genetic testing was performed in their second decade of life. Both patients' exomic sequencing test reported the mutation c.1129C >T (p.Arg377*) affecting exon 10 of the <i>CLCN1</i>, generating a premature stop codon. This mutation was described as pathogenic and observed in only one other patient in the United Kingdom.</p><p><strong>Conclusion: </strong>To our knowledge, these are the first cases of Becker's type myotonia congenita reported in Colombia. Increasing awareness of healthcare providers for this type of disease in the region could lead to the identification of undiagnosed patients. Limited availability of medical geneticists as well as genetic testing may be the cause of the lack of previous description of cases, in addition to the delay in the diagnosis of the patients. Further epidemiological studies can reveal underdiagnosed myotonias in the country and in the Latin-American region.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"14 ","pages":"473-479"},"PeriodicalIF":3.1,"publicationDate":"2021-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/11/01/tacg-14-473.PMC8687676.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39625793","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 for DEB by Detecting a Novel Family-Specific COL7A1 Mutation in Vietnam.","authors":"Sang Trieutien,&nbsp;Tam Vu Van,&nbsp;My Tran Ngoc Thao,&nbsp;Son Trinh The,&nbsp;Khoa Tran Van,&nbsp;Tung Nguyen Thanh,&nbsp;Tuan Tran Van,&nbsp;Hanh Nguyen Thi","doi":"10.2147/TACG.S344107","DOIUrl":"https://doi.org/10.2147/TACG.S344107","url":null,"abstract":"<p><strong>Background: </strong>Epidermolysis bullosa (EB) is a disorder characterized by the appearance of blisters, erosions and wounds in response to minimal trauma. The disease manifests with noticeable symptoms ranging from mild to severe, classified into four major types: epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), dystrophic epidermolysis bullosa (DEB) and Kindler syndrome. Preimplantation genetic diagnosis for the disease remains the only available option for families at risk for the recurrence of the disorder without having to terminate an ongoing pregnancy.</p><p><strong>Materials and methods: </strong>A novel <i>COL7A1</i> mutation was used to design primers for the polymerase chain reaction (PCR) to amplify the segment spanning the mutation in the family and their in-vitro fertilization (IVF) embryos. Then, the PCR products were sequenced with Sanger sequencing to detect the alteration in the allele, and some embryos would go through NGS-based preimplantation screening for chromosomal abnormalities.</p><p><strong>Results: </strong>The established protocol for EB detected mutant allele in 6/9 embryos (66.6%), while the remaining 3 embryos (33.4%) appeared to not carry any mutation. Only one among 3 embryos was recommended to be transferred into the mother's uterus.</p><p><strong>Conclusion: </strong>The established preimplantation genetic diagnosis procedure is helpful to families affected by epidermolysis bullosa caused by <i>COL7A1</i> mutations but wish to have healthy children.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"14 ","pages":"467-472"},"PeriodicalIF":3.1,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/32/95/tacg-14-467.PMC8668251.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39732352","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":"Novel Genetic Causes of Gastrointestinal Polyposis Syndromes.","authors":"Anne Marie Jelsig,&nbsp;Anna Byrjalsen,&nbsp;Majbritt Busk Madsen,&nbsp;Tine Plato Kuhlmann,&nbsp;Thomas van Overeem Hansen,&nbsp;Karin A W Wadt,&nbsp;John Gásdal Karstensen","doi":"10.2147/TACG.S295157","DOIUrl":"https://doi.org/10.2147/TACG.S295157","url":null,"abstract":"<p><p>Hereditary polyposis syndromes are characterized by a large number and/or histopathologically specific polyps in the gastrointestinal tract and a high risk of both colorectal cancer and extracolonic cancer at an early age. While the genes responsible for some of the syndromes, eg, <i>APC</i> in familial adenomatous polyposis and <i>STK11</i> in Peutz-Jeghers syndrome, have been known for decades, novel genetic causes have recently been detected that have shed light on the broader clinical spectrum of syndromes. Genetic diagnoses are important because they can facilitate a personalized surveillance program. Furthermore, at-risk members of the patient's family can be tested and enrolled in surveillance as needed. In some cases, prenatal diagnostics should be offered. In this paper, we describe the development in germline genetics of the hereditary polyposis syndromes over the last 10-12 years, their clinical characteristics, as well as how to implement genetic analyses in the diagnostic pipeline.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"14 ","pages":"455-466"},"PeriodicalIF":3.1,"publicationDate":"2021-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/85/tacg-14-455.PMC8637176.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39694285","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":"Genetic Testing in CYLD Cutaneous Syndrome: An Update.","authors":"Nikoletta Nagy,&nbsp;Anna Dubois,&nbsp;Marta Szell,&nbsp;Neil Rajan","doi":"10.2147/TACG.S288274","DOIUrl":"https://doi.org/10.2147/TACG.S288274","url":null,"abstract":"Abstract CYLD cutaneous syndrome (CCS) is an inclusive label for the inherited skin adnexal tumour syndromes Brooke–Spiegler Syndrome (BSS-OMIM 605041), familial cylindromatosis (FC – OMIM 132700) and multiple familial trichoepitheliomas (MFT-OMIM 601606). All three syndromes arise due to germline pathogenic variants in CYLD, a tumour suppressor gene (OMIM 605018). CCS is transmitted in an autosomal dominant pattern, and has variable expressivity, both of the three syndromic phenotypes, and of the severity of tumour burden. Age-related penetrance figures are not precisely reported. The first tumours typically appear during puberty and progressively accumulate through adulthood. Penetrance is typically high, with equal numbers of males and females affected. Genetic testing is important for confirmation of the clinical diagnosis, genetic counselling and family planning, including preimplantation diagnosis. Additionally, identified CCS patients may be eligible for future clinical trials of non-surgical pre-emptive interventions that aim to prevent tumour growth. In this update, we review the clinical presentations of germline and mosaic CCS. An overview of the germline pathogenic variant spectrum of patients with CCS reveals more than 100 single nucleotide variants and small insertions and deletions in coding exons, most frequently resulting in predicted truncation. In addition, a minority of patients have large deletions involving the CYLD gene, intronic pathogenic variants that affect splicing, or inversions. We discuss germline and somatic testing approaches. Somatic testing of tumour tissue, relevant in mosaic CCS, can reveal recurrently detected pathogenic variants when two or more tumours are tested. This can influence genetic testing of children, who may inherit this as a germline variant, and inform genetic counselling and prenatal diagnosis. Finally, we discuss testing technologies that are currently used, their benefits and limitations, and future directions for genetic testing in CCS.","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"14 ","pages":"427-444"},"PeriodicalIF":3.1,"publicationDate":"2021-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c3/30/tacg-14-427.PMC8566010.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39596940","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":"A Novel Intronic <i>KMT2D</i> Variant as a Cause of Kabuki Syndrome: A Case Report.","authors":"Erica Aristizábal,&nbsp;Lorena Diaz-Ordóñez,&nbsp;Estephania Candelo,&nbsp;Harry Pachajoa","doi":"10.2147/TACG.S317723","DOIUrl":"https://doi.org/10.2147/TACG.S317723","url":null,"abstract":"<p><p>Kabuki syndrome (KS) is an autosomal dominant genetic disorder in which most cases are caused by de novo mutations. KS type 1 is caused by mutations in <i>KMT2D</i> (OMIM: #147920) and is more common. KS type 2 is caused by mutations in <i>KDM6A</i> (OMIM: #300867). Both genes encode proteins that modify histones and are involved in epigenetic regulation. The enzyme histone-lysine N-methyltransferase 2D, the product of <i>KMT2D</i>, is expressed in most adult tissues and is essential for early embryonic development. The main clinical manifestations of KS include dysmorphic facial features, such as elongated palpebral fissures, eversion of the lateral third of the lower eyelids, and short nasal columella with a broad and depressed nasal tip. Additionally, patients also present with skeletal abnormalities, dermatoglyphic features, mild-to-moderate intellectual disability, hearing loss, and postnatal growth deficiency. We describe an 11-year-old girl from Colombia, who presented with characteristic clinical signs of KS. Genetic studies showed a <i>KMT2D</i> intronic variant (KMT2D NM_003482.3: c.511-2A> T) as a cause of KS.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"14 ","pages":"409-416"},"PeriodicalIF":3.1,"publicationDate":"2021-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/3d/tacg-14-409.PMC8502069.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39538444","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}