The Application of Clinical Genetics最新文献

{"title":"The role of <i>PAX9</i> promoter gene polymorphisms in causing hypodontia: a study in the Jordanian population.","authors":"Ahmed Abu-Siniyeh,&nbsp;Omar F Khabour,&nbsp;Arwa I Owais","doi":"10.2147/TACG.S183212","DOIUrl":"https://doi.org/10.2147/TACG.S183212","url":null,"abstract":"<p><strong>Background: </strong>The congenital absence of one or few teeth, hypodontia, is considered one of the utmost dental ageneses in human beings. Several genes have been shown to be involved in the development of hypodontia such as paired box gene 9 (<i>PAX9</i>). The expression of <i>PAX9</i> is controlled by several polymorphic elements in the promoter region of the gene on 14q13.3 locus. The aim of this study was to find any association between <i>PAX9</i> c.-912T>C (rs2073247) and c.-1031G>A (rs2073244) promoter polymorphisms and the development of hypodontia among the Jordanian population.</p><p><strong>Methods: </strong>Genotyping of the polymorphisms in 72 unrelated subjects with hypodontia was performed using PCR-restriction fragment length polymorphism (RFLP) technique and compared with that of 72 normal healthy unrelated control individuals.</p><p><strong>Results: </strong>The hypodontia group had a significantly higher -1031GG genotype (<i>P</i><0.01) and a significantly lower -912TC genotype (<i>P</i><0.01) compared with the control group. The results suggest that the transcriptional activity of <i>PAX9</i> gene is affected by polymorphisms in the promoter region of this gene and is associated with hypodontia phenotype.</p><p><strong>Conclusion: </strong>The rs2073247) and rs2073244 promoter polymorphisms of PAX9 might play a role in the development of hypodontia in the Jordanian population.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 ","pages":"145-149"},"PeriodicalIF":3.1,"publicationDate":"2018-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S183212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36816142","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 genetics of congenital central hypoventilation syndrome: clinical implications.","authors":"John Bishara,&nbsp;Thomas G Keens,&nbsp;Iris A Perez","doi":"10.2147/TACG.S140629","DOIUrl":"https://doi.org/10.2147/TACG.S140629","url":null,"abstract":"<p><p>Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder of the autonomic nervous system (ANS) and respiratory control. This disorder, formerly referred to as Ondine's curse, is due to a mutation in the <i>PHOX2B</i> gene that affects the development of the neural crest cells. CCHS has an autosomal dominant pattern of inheritance. Majority of the patients have a polyalanine repeat mutation (PARM) of the <i>PHOX2B</i>, while a small group has non-PARM (NPARM). Knowledge of the patient's <i>PHOX2B</i> gene mutation helps predict a patient's clinical presentation and outcome and aids in anticipatory management of the respiratory and ANS dysfunction.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 ","pages":"135-144"},"PeriodicalIF":3.1,"publicationDate":"2018-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S140629","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36810775","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":"Potential oligogenic disease of mental retardation, short stature, spastic paraparesis, and osteopetrosis.","authors":"Abdulaziz Alsemari,&nbsp;Mohanned Alsuhaibani,&nbsp;Rawabi Alhathlool,&nbsp;Bayan Mamdouh Ali","doi":"10.2147/TACG.S172176","DOIUrl":"https://doi.org/10.2147/TACG.S172176","url":null,"abstract":"<p><p>The interaction of multiple genetic factors, as opposed to monogenic inheritance, has been suspected to play a role in many diseases. This interaction has been described as an oligogenic inheritance model, which may be a useful tool in explaining certain clinical observations. The purpose of this study was to search for novel genetic defects among members of a family with traits that include mental retardation, short stature, osteopetrosis, calcification of basal ganglia, and thinning of the corpus callosum. In the index case (111-4), we identified four homozygous mutations: chromosome 8, intron2 (c.232+1G>A) at CA2 gene; chromosome 15, exon 32 (c.6100C>T) at the SPG11; chromosome 5, exon 11 (c.1015G>A) at the MCCC2; and chromosome 9, exon 9 (C.1193g>t) at the LARP gene. The mutations were confirmed by Sanger sequencing, and both parents were observed to be heterozygous for the four mutations. A moderately affected sister of the index case was homozygous for only three mutations in CA2, LARP, and Mccc2, while a nonaffected sister was heterozygous for three mutations in CA2, LARP, and MCCC2 and negative for SPG11. The clinical features of the two affected sisters can be explained distinctively by each homozygous mutation in an oligogenic pattern of inheritance. This family represents an example of an oligogenic pattern of inheritance of mental retardation, short stature, spastic paraparesis, and osteopetrosis.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 ","pages":"129-134"},"PeriodicalIF":3.1,"publicationDate":"2018-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S172176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36747979","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 mitochondrial DNA copy number with self-rated health status.","authors":"Paul Y Takahashi,&nbsp;Gregory D Jenkins,&nbsp;Benjamin P Welkie,&nbsp;Shannon K McDonnell,&nbsp;Jared M Evans,&nbsp;James R Cerhan,&nbsp;Janet E Olson,&nbsp;Stephen N Thibodeau,&nbsp;Mine S Cicek,&nbsp;Euijung Ryu","doi":"10.2147/TACG.S167640","DOIUrl":"https://doi.org/10.2147/TACG.S167640","url":null,"abstract":"<p><strong>Purpose: </strong>In aging adults, mitochondrial dysfunction may be an important contributor. We evaluated the association between mitochondrial DNA (mtDNA) copy number, which is a biomarker for mitochondrial function, and self-rated health status.</p><p><strong>Patients and methods: </strong>We conducted a cross-sectional study of patients enrolled within the Mayo Clinic Biobank. We utilized the questionnaire and sequence data from 944 patients. We examined the association between mtDNA copy number and self-rated health status with 3 collapsed categories for the latter variable (excellent/very good, good, and fair/poor). For analysis, we used proportional odds models after log-transforming mtDNA copy number, and we adjusted for age and sex.</p><p><strong>Results: </strong>We found the median age at enrollment was 61 years (25th-75th percentile: 51-71), and 64% reported excellent or very good health, 31% reported good health, and 6% reported fair/poor health. Overall, the median mtDNA copy number was 88.9 (25th-75th percentile: 77.6-101.1). Higher mtDNA copy number was found for subjects reporting better self-rated health status after adjusting for age, sex, and comorbidity burden (OR =2.3 [95% CI: 1.2-4.5] for having better self-rated health for a one-unit increase in log-transformed mtDNA copy number).</p><p><strong>Conclusion: </strong>We found that a higher mtDNA copy number is associated with better self-rated health status after adjustment for age, sex, and comorbidity burden. The current study implies that mtDNA copy number may serve as a biomarker for self-reported health. Further studies, potentially including cohort studies, may be required.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 ","pages":"121-127"},"PeriodicalIF":3.1,"publicationDate":"2018-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S167640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36735716","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":"Pena-Shokeir syndrome: current management strategies and palliative care.","authors":"Sumaiya Adam,&nbsp;Melantha Coetzee,&nbsp;Engela Magdalena Honey","doi":"10.2147/TACG.S154643","DOIUrl":"https://doi.org/10.2147/TACG.S154643","url":null,"abstract":"<p><p>Pena-Shokeir syndrome (PSS) type 1, also known as fetal akinesia deformation sequence, is a rare genetic syndrome that almost always results in intrauterine or early neonatal death. It is characterized by markedly decreased fetal movements, intrauterine growth restriction, joint contractures, short umbilical cord, and features of pulmonary hypoplasia. Antenatal diagnosis can be difficult. Ultrasound features are varied and may overlap with those of Trisomy 18. The poor prognosis of PSS is due to pulmonary hypoplasia, which is an important feature that distinguishes PSS from arthrogryposis multiplex congenital without pulmonary hypoplasia, which has a better prognosis. If diagnosed in the antenatal period, a late termination of pregnancy can be considered following ethical discussion (if the law allows). In most cases, a diagnosis is only made in the neonatal period. Parents of a baby affected with PSS require detailed counseling that includes information on the imprecise recurrence risks and a plan for subsequent pregnancies.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 ","pages":"111-120"},"PeriodicalIF":3.1,"publicationDate":"2018-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S154643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36735715","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":"Aortic calcification in Gaucher disease: a case report.","authors":"Saud Alsahli,&nbsp;Dalal K Bubshait,&nbsp;Zuhair A Rahbeeni,&nbsp;Majid Alfadhel","doi":"10.2147/TACG.S180995","DOIUrl":"https://doi.org/10.2147/TACG.S180995","url":null,"abstract":"<p><p>Gaucher disease is the most common sphingolipid storage disease and is present in all ethnic groups. Its symptoms span all systems including the cardiovascular system. The health care provider should be vigilant regarding this potentially fatal complication. Gaucher disease type IIIC has been linked to causing oculomotor apraxia and cardiac calcification. We report a Saudi girl who developed valvular and aortic calcification in late childhood and died as a result of her cardiovascular complications. This report further strengthens the association and reminds the clinicians that patients with D409H mutation need echocardiographic evaluation annually.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 ","pages":"107-110"},"PeriodicalIF":3.1,"publicationDate":"2018-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S180995","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36661964","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":"IRS-1 genetic polymorphism (r.2963G>A) in type 2 diabetes mellitus patients associated with insulin resistance.","authors":"Anas A Yousef,&nbsp;Eman G Behiry,&nbsp;Wafaa M Abd Allah,&nbsp;Ahmed M Hussien,&nbsp;Abdelmoneam A Abdelmoneam,&nbsp;Mahmoud H Imam,&nbsp;Doaa M Hikal","doi":"10.2147/TACG.S171096","DOIUrl":"https://doi.org/10.2147/TACG.S171096","url":null,"abstract":"<p><strong>Background: </strong>Insulin receptor substrate (IRS) molecules are key mediators in insulin signaling. Several polymorphisms in the IRS genes have been identified, but only the Gly to Arg 972 substitution of IRS-1 seems to have a pathogenic role in the development of type 2 diabetes mellitus (T2DM). Many polymorphisms described in IRS-1 gene, especially Gly972Arg substitution, are shown to be associated with insulin resistance (IR) in T2DM.</p><p><strong>Subjects and methods: </strong>This prospective case-control study was performed during the period from November 2014 to May 2015. All patients were selected from the Department of Internal Medicine and were screened for eligibility for this study. Subjects were divided into two groups: first group consisted of 100 T2DM patients; second group consisted of 120 nondiabetic controls. First group was further divided into two subgroups: 66 IR patients and 34 insulin-sensitive (IS) patients (homeostatic model assessment [HOMA] was performed). Restriction fragment length polymorphism (RFLP) was performed using specific primers for scanning single-nucleotide polymorphisms (SNPs) such as Gly972Arg (rs1801278 SNP).</p><p><strong>Results: </strong>Taking GG genotype and G allele as references, GA, GA+AA genotypes and A allele showed significantly higher frequency in the T2DM group when compared to the control group, with higher risk to develop T2DM in healthy controls. Taking GG as a reference, rs1801278GA+AA genotype and A allele showed significantly higher proportion in IR when compared to IS, with higher risk to develop IR in T2DM patients. Logistic regression analysis showed that higher FBG, fasting plasma insulin (FPI), HOMA-IR, GA+AA genotypes were associated with higher risk to develop IR in univariable analysis.</p><p><strong>Conclusion: </strong>IRS-1 genetic factor may be a significant genetic determinant for IR in T2DM patients during severe/acute-phase hyperglycemia.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 ","pages":"99-106"},"PeriodicalIF":3.1,"publicationDate":"2018-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S171096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36574274","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 trio-based exome sequencing in the elucidation of the genetic basis of isolated syndromic intellectual disability: illustrative cases.","authors":"Thaise Nr Carneiro,&nbsp;Ana Cv Krepischi,&nbsp;Silvia S Costa,&nbsp;Israel Tojal da Silva,&nbsp;Angela M Vianna-Morgante,&nbsp;Renan Valieris,&nbsp;Suzana Am Ezquina,&nbsp;Debora R Bertola,&nbsp;Paulo A Otto,&nbsp;Carla Rosenberg","doi":"10.2147/TACG.S165799","DOIUrl":"https://doi.org/10.2147/TACG.S165799","url":null,"abstract":"<p><strong>Introduction: </strong>Exome sequencing is recognized as a powerful tool for identifying the genetic cause of intellectual disability (ID). It is uncertain, however, whether only the exome of the proband should be sequenced or if the sequencing of parental genomes is also required, and the resulting increase in diagnostic yield justifies the increase in costs.</p><p><strong>Patients and methods: </strong>We sequenced the exomes of eight individuals with sporadic syndromic ID and their parents.</p><p><strong>Results and discussion: </strong>Likely pathogenic variants were detected in eight candidate genes, namely homozygous or compound heterozygous variants in three autosomal genes (<i>ADAMTSL2</i>, <i>NALCN</i>, <i>VPS13B</i>), one in an X-linked gene (<i>MID1</i>), and de novo heterozygous variants in four autosomal genes (<i>RYR2, GABBR2</i>, <i>CDK13</i>, <i>DDX3X</i>). Two patients harbored rare variants in two or more candidate genes, while in three other patients no candidate was identified. In five probands (62%), the detected variants explained their clinical findings. The causative recessive variants would have led to diagnosis even without parental exome sequencing, but for the heterozygous dominant ones, the exome trio-based approach was fundamental in the identification of the de novo likely pathogenic variants.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 ","pages":"93-98"},"PeriodicalIF":3.1,"publicationDate":"2018-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S165799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36455229","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":"Clinical features related to xeroderma pigmentosum in a Brazilian patient diagnosed at advanced age.","authors":"Marina Guinda Ribeiro,&nbsp;Gabriella Lucato Zunta,&nbsp;Jéssica Silva Santos,&nbsp;Aparecida Machado Moraes,&nbsp;Carmen Silvia Passos Lima,&nbsp;Manoela Marques Ortega","doi":"10.2147/TACG.S155083","DOIUrl":"https://doi.org/10.2147/TACG.S155083","url":null,"abstract":"<p><p>Xeroderma pigmentosum is a rare autosomal recessive genetic disease characterized by extreme sensitivity due to solar radiation and deficiency in excision repair DNA. Those factors promote a set of skin abnormalities such as keratosis, hyperpigmentation, tumors in areas exposed to sunlight, and ocular and, eventually, neurological disorders. In the present review, we summarize the main clinical features related to a case of xeroderma pigmentosum in a man who was not diagnosed until he was 45 years old.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 ","pages":"89-92"},"PeriodicalIF":3.1,"publicationDate":"2018-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S155083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36414851","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":"Independent of DAZL-T54A variant and AZF microdeletion in a sample of Egyptian patients with idiopathic non-obstructed azoospermia.","authors":"Mohammed M El Shafae,&nbsp;Jehan H Sabry,&nbsp;Eman G Behiry,&nbsp;Hanan H Sabry,&nbsp;Mona A Salim,&nbsp;Alaaeldin G Fayez","doi":"10.2147/TACG.S158297","DOIUrl":"https://doi.org/10.2147/TACG.S158297","url":null,"abstract":"<p><strong>Background: </strong>The microdeletion events that occur in the Y chromosome-azoospermia factor (<i>AZF</i>) region may lead to dyszoospermia. Also, the deleted azoospermia (<i>DAZ</i>) gene on AZFc and autosomal deleted azoospermia like gene (<i>DAZL</i>) are suggested to represent impairment, so it is interesting to determine the independency pattern of the <i>AZF</i> region and <i>DAZL</i> gene in azoospermic patients.</p><p><strong>Aim: </strong>To study the molecular characterization of <i>AZFc</i> and <i>DAZL</i> in 64 idiopathic non-obstructed azoospermia patients and 30 sexually reproductive men.</p><p><strong>Methods: </strong>SYBR Green I (Q-PCR) and AZF-STS analysis was used for <i>DAZ</i> gene, and SNV-PCR and confirmative Sanger sequencing for <i>DAZ</i>L gene.</p><p><strong>Results: </strong>The present study observed that 15.6% had <i>AZF</i>c microdeletion, out of which 10% had <i>DAZ1/2</i> deletion, and no <i>T54A</i> variant in the <i>DAZL</i> gene was found.</p><p><strong>Conclusion: </strong>In the current work, the novelty is that spermatogenic impairment phenotype, present with <i>AZFc</i> microdeletions, is independent of the <i>T54A</i> variant in the <i>DAZL</i> gene, and <i>AZFc</i> microdeletions could be a causative agent in spermatogenic impairment.</p>","PeriodicalId":506374,"journal":{"name":"The Application of Clinical Genetics","volume":"11 ","pages":"81-87"},"PeriodicalIF":3.1,"publicationDate":"2018-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/TACG.S158297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36348358","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}