Application of Clinical Genetics最新文献

{"title":"The Many Faces of Arrhythmogenic Cardiomyopathy: An Overview.","authors":"Hanna J Tadros, Christina Y Miyake, Debra L Kearney, Jeffrey J Kim, Susan W Denfield","doi":"10.2147/TACG.S383446","DOIUrl":"https://doi.org/10.2147/TACG.S383446","url":null,"abstract":"<p><p>Arrhythmogenic cardiomyopathy (AC) is a disease that involves electromechanical uncoupling of cardiomyocytes. This leads to characteristic histologic changes that ultimately lead to the arrhythmogenic clinical features of the disease. Initially thought to affect the right ventricle predominantly, more recent data show that it can affect both the ventricles or the left ventricle alone. Throughout the recent era, diagnostic modalities and criteria for AC have continued to evolve and our understanding of its clinical features in different age groups as well as the genotype to the phenotype correlations have improved. In this review, we set out to detail the epidemiology, etiologies, presentations, evaluation, and management of AC across the age continuum.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"16 ","pages":"181-203"},"PeriodicalIF":3.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71487077","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":"Evaluating the Association Between Genetic Polymorphisms Related to Homocysteine Metabolism and Unexplained Recurrent Pregnancy Loss in Women.","authors":"Nhat Nguyen Ngoc, My Tran Ngoc Thao, Sang Trieu Tien, Son Vu Tung, Hoang Le, Hung Ho Sy, Tung Nguyen Thanh, Son Trinh The","doi":"10.2147/TACG.S365281","DOIUrl":"10.2147/TACG.S365281","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the relationship between unexplained recurrent pregnancy loss (URPL) and polymorphisms of homocysteine metabolism-related genes in women.</p><p><strong>Materials and methods: </strong>A case-control study included 90 women with two or more consecutive unexplained pregnancy losses and 92 controlled women without miscarriage history; the female participants were in the age category of 18-35 years. The high-resolution melting technique was used to detect the single-nucleotide variants related to homocysteine metabolism disorder, namely <i>MTHFR</i> C677T, <i>MTHFR</i> A1298C, <i>MTR</i> A2756G, and <i>MTRR</i> A66G polymorphism.</p><p><strong>Results: </strong>The <i>MTHFR</i> C677T polymorphism had significantly correlation with URPL. Indeed, the frequency of the677T allele and genotypes (677CT, 677TT) in the URPL group was significantly higher than that in the control group (p < 0.05). However, the allele, as well as genotype distribution of <i>MTHFR</i> A1298C, <i>MTR</i> A2756G, and <i>MTRR</i> A66G polymorphisms showed no significant difference (p > 0.05). <i>MTHFR</i> 677CT-1298AC genotype combination led to a 9.0-fold increased risk of URPL (OR 9.0; 95% CI, 2.25-35.99; p = 0.001), while the risk increased 10.0-fold (OR 10.0; 95% CI, 1.8-55.53; p = 0.008) when participants had more than the 3 variant loci.</p><p><strong>Conclusion: </strong>The <i>MTHFR</i> C677T polymorphism was a risk factor for URPL, and determining the <i>MTHFR</i> C677T polymorphism had a potential prediction of URPL risk. Moreover, the <i>MTHFR</i> C677T and <i>MTHFR</i> A1298C joint mutants might have a synergistic effect on URPL. Conversely, there is a lack of evidence suggesting the URPL risk of <i>MTHFR</i> A1298C, <i>MTR</i> A2756G, and <i>MTRR</i> A66G polymorphisms.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"15 1","pages":"55-62"},"PeriodicalIF":2.6,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44886146","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":"Prominent Mutation of Intron 22 Inversion in Sporadic Hemophilia: Is It Worth the Antenatal Screening?","authors":"W. Sasanakul, A. Chuansumrit, N. Sirachainan, P. Kadegasem","doi":"10.2147/TACG.S363132","DOIUrl":"https://doi.org/10.2147/TACG.S363132","url":null,"abstract":"Background Adequate replacement for patients with hemophilia is costly, especially in countries with limited resources. Objective Factor VIII gene mutations among Thai patients with hemophilia A were analyzed for the most common mutation. The cost-effectiveness of finding one female without family history of hemophilia possessing the most common factor VIII mutation was compared with the cost of treating one patient with hemophilia. Methods In all, 109 unrelated patients with hemophilia A, defined as sporadic cases (n=58) and hereditary cases (n=51), were enrolled for genotypic analysis. Results Intron 22 inversion was prominently found in 34 sporadic (58.6%) and 27 hereditary (51.9%) cases. The screening for intron 22 inversion among females without family history of hemophilia at antenatal care has been optionally suggested. A female with a positive result will undergo further prenatal diagnosis of hemophilia in her male offspring. On the contrary, a female with a negative test result remains at risk to have a hemophiliac son caused by other factor VIII gene mutations not included in the screening but the risk is not as high as intron 22 inversion. Although the screening of factor VIII mutation among females without family history of hemophilia is against the current practice, it has been initiated due to the inadequate treatment provided to patients with hemophilia in countries with limited resources. The study calculated approximately one female with intron 22 inversion would exist among 17,064 females without family history of hemophilia. The cost of screening (194,870 USD) was much less than that of treating one patient with hemophilia from birth to 40 years of age by the current regimen (378,000 USD). Conclusion Implementing antenatal screening of intron 22 inversion among females without family history of hemophilia is optionally suggested, especially in economically less-developed countries with inadequate treatment service for patients with hemophilia.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"15 1","pages":"49 - 54"},"PeriodicalIF":3.1,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41392044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Genetic Screening of Neonatal Intensive Care Units: Hyperbilirubinemia as an Example","authors":"Yuqi Yang, Yu Wang, Lingna Zhou, W. Long, Binsheng Yu, Huaiyan Wang","doi":"10.2147/TACG.S362148","DOIUrl":"https://doi.org/10.2147/TACG.S362148","url":null,"abstract":"Objective To explore the clinical value of newborn genomic screening (nGS) for neonatal intensive care units (NICU) infants (taking neonatal hyperbilirubinemia as an example). Methods Dried blood spots (DBSs) were collected after 72 hours of birth. The tandem mass spectrometry (TMS) screening and Angel Care genomic screening (GS, based on Targeted next-generation sequencing) were performed at the same time. Results Ninety-six hyperbilirubinemia newborns were enrolled in this study and none was identified with inborn errors of metabolism (IEM) by TMS, while 6 infants (6.25%, 6/96) were suspected to have a genetic disorder by Angel Care, including 2 cases of glucose-6-phosphate dehydrogenase deficiency (G6PD), and 1 case of maple syrup urine disease type 1B (MSUD1B), autosomal recessive deafness 1A (DFNB1A), Leber hereditary optic neuropathy (LHON), thyroid dyshormonogenesis 6 (TDH6) each. In addition, 44 infants (45.8%) were detected having at least one variant which conferred a carrier status for a recessive childhood-onset disorder. A total of 33 out of 60 variants (55.0%) reported for carrier status were pathogenic (P), 24 (40.0%) were likely pathogenic (LP), and 3 variants were variant of uncertain significance (VUS). Top six common genes of carrier status were GJB2, DUOX2, PRODH, ATP7B, SLC12A3, SLC26A4. Two newborns showed abnormalities in elementary screening of TMS, but were confirmed as false positive after recall. Their results of Angel Care did not found abnormality. Conclusion Using neonatal hyperbilirubinemia as an example, genome sequencing screening can find more evidence of genetic variation in NICU newborns, and “Angel Care” is an effective method.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"15 1","pages":"39 - 48"},"PeriodicalIF":3.1,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44952510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CTLA-4 CT-60 A/G and CTLA-4 1822 C/T Gene Polymorphisms in Indonesians with Type 1 Diabetes Mellitus","authors":"N. Rochmah, M. Faizi, Suhasta Nova, R. A. Setyoningrum, S. Basuki, A. Endaryanto","doi":"10.2147/TACG.S359158","DOIUrl":"https://doi.org/10.2147/TACG.S359158","url":null,"abstract":"Introduction CTLA-4 gene polymorphism plays an important role in children with type 1 diabetes mellitus (T1DM). However, data on this subject vary among different races and ethnics. Purpose To analyze CTLA-4 CT-60 A/G and CTLA-4 1822 C/T gene polymorphism among children with T1DM compared to control. Patients and Methods The CTLA-4 CT-60 A/G and CTLA-4 1822 C/T gene polymorphism in children with T1DM using polymerase chain reaction-restriction fragment length polymorphism in 25 T1DM and 25 controls. The inclusion criteria were patients regularly controlled at the Pediatric Endocrine Outpatient Clinic of Dr. Soetomo Hospital, aged 4–18 years and willing to join this study and the exclusion criteria were T1DM patients hospitalized in the pediatric intensive care unit. In the control group, the inclusion criteria were healthy children, aged 4–18 years and willing to join this study. The exclusion criteria included children with ongoing infection, history of other autoimmune diseases, allergies, or malignancy. Results The mean age was 12.48 years old, and the mean of T1DM onset was 9.28 years old. The CTLA-4 1822 T allele observed in 62% T1DM and 56% in control (p = 0.388, OR = 0.78, 95% CI = 0.44–1.37) and CTLA-4 CT-60 G allele observed in 52% T1DM and 58% in control (p = 0.393, OR = 1.27, 95% CI = 0.73–2.22). The C/T genotypes was significantly higher in control group (p = 0.045, OR = 3.27, 95% CI = 1.00–10.62). The A/G genotypes was commonly found in control group (p = 0.765, OR = 1.20, 95% CI = 0.37–3.86). The Javanese was the dominant ethnic group in our study. Conclusion The frequency of CTLA-4 CT-60 A/G polymorphism almost equivalent in T1DM and control group. However, CTLA-4 1822 C/T polymorphism was more prevalent in the control group; thus, this genotype may have a protective effect against T1DM.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"15 1","pages":"19 - 25"},"PeriodicalIF":3.1,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42873602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCR2 Genetic Polymorphism And Its Potential Effect On HIV Acquisition In A Population Of Children Living In The Northern Region Of Cameroon","authors":"M. Ngoufack, C. Nkenfou, Barbara Atogho Tiedeu, L. Mouafo, B. Dambaya, E. Ndzi, C. Kouanfack, G. Nguefack-Tsague, W. Mbacham, A. Ndjolo","doi":"10.2147/TACG.S202498","DOIUrl":"https://doi.org/10.2147/TACG.S202498","url":null,"abstract":"Background and objectives The association of chemokine receptor-2 (CCR2) polymorphism with HIV transmission or disease progression remains highly controversial. The role of CCR2-64I allele in HIV infection may differ from one population to another because of their genetic background. The objectives of this study were to characterize the CCR2 genetic polymorphism and to determine its potential effect in HIV acquisition in children living in the Northern Region of Cameroon. Materials and methods A cross-sectional study was carried out in five health facilities in the Northern region of Cameroon. DNA was extracted from the Buffy coat of each participant using the QIAamp®DNA mini kit. The DNA extract was then subjected to polymorphic analyses. CCR2 genotypes were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The Chi-Squared test was used for the assessment of the Hardy-Weinberg equilibrium. Results A total of 134 children under 15 years comprised of 38 HIV-exposed infected (28.36%) and 96 HIV-exposed un-infected (71.64%) participants were recruited. Prevalences of 44.78% wild type homozygous, 48.52% heterozygous and 6.7% mutant homozygous alleles were found in the overall population. An allelic frequency of 29.69% for the mutant allele CCR2-64I was found in HIV-exposed un-infected individuals as compared to 34.21% in HIV-infected children (p=0.47). Conclusion The CCR2-64I allele is relatively common in the Northern Region of Cameroon, with a similar distribution among HIV-exposed un-infected and infected children. As this allele alone does not seem to confer protection against HIV-1 infection, further studies using genotype-combination of CCR2 polymorphism and other single nucleotide polymorphisms would be of great relevance in both HIV prevention and novel therapeutic strategies.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"229 - 234"},"PeriodicalIF":3.1,"publicationDate":"2019-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S202498","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48529744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Candidate Gene Analysis Of Alopecia Areata In Jordanian Population Of Arab Descent: A Case–Control Study","authors":"L. Al-Eitan, Rawan O. Al Momani, Khalid K Al Momani, Ahmad M Al Warawrah, Hanan A. Aljamal, M. Alghamdi, A. Muhanna, Firas A. Al-qarqaz","doi":"10.2147/TACG.S226664","DOIUrl":"https://doi.org/10.2147/TACG.S226664","url":null,"abstract":"Background Alopecia areata (AA) is a non-cicatricial patchy hair loss on the scalp, face or other parts of the body. AA was found to be responsive to immunosuppressive therapies, a finding that supports an autoimmune basis for the disease. Several genetic studies have shown the significance of immunological factors as key genetic components in AA. Objective In this study, we aimed to investigate the genetic association of 7 single-nucleotide polymorphisms (SNPs) within five candidate genes including TAP1, CXCL1, CXCL2, HSPA1B, and TNFα with AA susceptibility in the Jordanian Arab population. Methods A case–control genetic association study conducted in 152 patients and 150 healthy individuals was performed using the sequenom MassARRAY system (iPLEX GOLD) to genotype the selected SNPs. Results rs1800629 SNP of the TNFα gene was significantly associated with AA in the heterozygous and rare homozygous genotypes (P=0.022 and P=0.0079, respectively) with no linkage of the TAP1, CXCL1, CXCL2 and HSPA1B variants. Conclusion This is the first study of its kind among the Jordanian population providing evidence of genetic association of the TNFα with AA susceptibility. Further genetic studies on Arab descent including other variants are required to clarify and strengthen the association of these genes with susceptibility to develop AA.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"221 - 228"},"PeriodicalIF":3.1,"publicationDate":"2019-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S226664","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45577408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC22A1 And ATM Genes Polymorphisms Are Associated With The Risk Of Type 2 Diabetes Mellitus In Western Saudi Arabia: A Case-Control Study","authors":"Rana M Altall, S. Qusti, Najlaa Filimban, A. Alhozali, N. A. Alotaibi, A. Dallol, A. Chaudhary, S. Bakhashab","doi":"10.2147/TACG.S229952","DOIUrl":"https://doi.org/10.2147/TACG.S229952","url":null,"abstract":"Introduction Type 2 diabetes mellitus (T2DM) is a major global health problem that is progressively affected by genetic and environmental factors. The aim of this study is to determine the influence of solute carrier family 22 member 1 (SLC22A1) rs628031 and rs461473, and ataxia telangiectasia mutated (ATM) rs11212617 polymorphisms on the risk of T2DM in Saudi Arabia by considering many parameters associated with glycemic control of T2DM, such as body mass index (BMI), fasting blood glucose, glycated hemoglobin (HbA1c), and triglyceride. Methods In a case-control study, genomic DNA from controls and diabetic groups was isolated and genotyped for each single-nucleotide polymorphism. Results There were significant correlations between T2DM and both BMI and HbA1c. Significant associations between G/G and A/G genotypes of rs628031 and rs461473 variants of SLC22A1 and high levels of HbA1c were detected. Therefore, G was predicted to be the risk allele among the assessed SLC22A1 variants. A significant correlation was observed between A/A and A/C genotypes of the rs11212617 polymorphism of ATM and elevated HbA1c. Relative risk calculation confirmed A to be the risk allele in the T2DM population. Conclusion Our study showed the risk of the assessed SLC22A1 and ATM variants on glycemic control parameters in diabetic patients.","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"213 - 219"},"PeriodicalIF":3.1,"publicationDate":"2019-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S229952","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43610477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM5α 136Q, CCR5 Promoter 59029G And CCR264I Alleles Impact The Progression Of HIV In Children And Adolescents.","authors":"Béatrice Dambaya, Céline Nguefeu Nkenfou, Linda Mekue, Georges Této, Nicole Ngoufack, Georgia Ambada, Njiokou Flobert, Vittorio Colizzi, Ndjolo Alexis","doi":"10.2147/TACG.S205335","DOIUrl":"10.2147/TACG.S205335","url":null,"abstract":"<p><strong>Background: </strong>Children show various degrees of vulnerability regarding HIV infection and disease progression. This disparity presents challenges for the follow-up of infected children. Here we investigated reasons behind this variability focusing on some host-related HIV genes.</p><p><strong>Methods: </strong>We screened 570 Cameroonian children and adolescents, aged 1 to 19 years old. Among them, 137 were followed over 4 years, from 2010 to 2015. Upon signing a proxy consent, children and adolescents were classified according to their age, CD4 count, viral load and clinical symptoms as long-term non-progressors (LTNP), slow progressors (SP) and rapid progressors (RP). Their blood was collected every 6 months and used for biological and host genetic polymorphism analyses. Five genes were genotyped: <i>Trim5α (R136Q), CCR5</i> promoter <i>59029G, CCR2-64I, SDF 3'A</i> and <i>CCR5-Δ32</i>. Exposed non-infected (HEU) and unexposed HIV negative children (HNEU) were recruited as control groups.</p><p><strong>Results: </strong>Among the 5 genes studied, the protective allele of Trim5α (R136Q) was present in all LTNP and in 72.34% and 2.56% of SP and RP, respectively (p<0.0001). The CCR5 promoter 59029G/G was also more present in LTNP and SP than in RP (p=0.02; p=0.04). The protective CCR2-64I homozygous genotype was almost absent in all groups, only the heterozygous genotype was present with a significant difference between RP vs SP (p=0.0001), and SP vs LTNP (p=0.0002). The CCR2-∆32 was completely absent either as homozygous or heterozygous genotype. It was a monomorphic allele. SDF 3'A was almost present as homozygous wild-type genotype in our study population and was associated neither to disease acquisition nor to disease progression.</p><p><strong>Conclusion: </strong>Among the 5 genes described in the study, Trim 5α (R136Q), CCR5 promoter 59029G and CCR2V64I alleles were associated to the progression of HIV infection in children and adolescents.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 1","pages":"203-211"},"PeriodicalIF":2.6,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42679472","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":"Update On The Clinical Perspectives And Care Of The Child With 47,XXY (Klinefelter Syndrome).","authors":"Carole A Samango-Sprouse,&nbsp;Debra R Counts,&nbsp;Selena L Tran,&nbsp;Patricia C Lasutschinkow,&nbsp;Grace F Porter,&nbsp;Andrea L Gropman","doi":"10.2147/TACG.S180450","DOIUrl":"https://doi.org/10.2147/TACG.S180450","url":null,"abstract":"<p><p>47,XXY (Klinefelter syndrome [KS]) is the most common sex chromosomal aneuploidy (1:660), yet, despite this, only 25% of the males are ever diagnosed. Males with 47,XXY present with characteristic symptoms throughout their lifetime with typical physical and neurodevelopmental manifestations focused in growth, cognitive development, endocrine function, and reproduction. Studies have demonstrated that optimal outcomes are dependent on early detection combined with consistent and targeted neurodevelopmental treatment throughout the lifespan. During infancy and into the preschool years, individuals with 47,XXY commonly face deficits in growth and development in the areas of early hormonal, motor, speech, and behavioral development. As they transition into school, the primary neurodevelopmental concerns include language difficulty, executive dysfunction, behavior, and learning and reading deficits. Adults with 47,XXY often present with taller than average height, low levels of fertility, azoospermia, and elevated gonadotropin levels. These presentations may persist from early childhood through adulthood but can be mitigated by appropriate interventions. Early neurodevelopmental and hormonal treatment has been shown to have a minimizing effect on the physical and neurodevelopmental manifestations in individuals with 47,XXY. With innovative and current research studies, the features common to the neurodevelopmental profile of 47,XXY have been further expanded and defined. Further research is necessary to elucidate and understand the relationship between the brain, behavior, and the phenotypic profile of 47,XXY.</p>","PeriodicalId":39131,"journal":{"name":"Application of Clinical Genetics","volume":"12 ","pages":"191-202"},"PeriodicalIF":3.1,"publicationDate":"2019-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S180450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215366","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}