scholarly journals Molecular-genetic and phenotypic characteristics of desmoid-type fibromatosis

2019 ◽  
pp. 9-15
Author(s):  
T.A. Muzaffarova ◽  
O.V. Novikova ◽  
I.Yu. Sachkov ◽  
F.M. Kipkeeva ◽  
E.K. Ginter ◽  
...  
Keyword(s):  
Clinical Course ◽  
Age Of Onset ◽  
Molecular Genetic ◽  
Germline Mutations ◽  
Apc Gene ◽  
Phenotypic Characteristics ◽  
Potential Significance ◽  
Desmoid Fibromatosis ◽  
Apc Mutations ◽  
Sporadic Tumors

Desmoid-type fibromatosis (DF) is a rare mesenchymal tumor occurring in only 2 to 4 people per 1,000,000 population a year. Desmoid tumors are either seen sporadically or in individuals with familial adenomatous polyposis (FAP). The etiology of sporadic DF is uncertain. The aim of this study was to estimate the potential significance of germline mutations in the APC gene in patients with sporadic DF. APC exons were amplified, studied using conformation sensitive gel electrophoresis and then Sanger-sequenced. The obtained data were processed in Statistica 10. Mutations were detected in 6 (12%) of 51 participants with sporadic DF. Those 6 patients shared a typical DF phenotype characterized by early age of onset (5.8 years on average, in contrast to the patients without APC mutations, who developed DF at 19 years of age; p = 0.02), severe clinical course, multifocal localization on the trunk, and poor prognosis. All of the detected APC mutations were localized to the 3'-end of the gene. For the purpose of comparison, we analyzed a sample of 12 patients with FAP-associated DF. Of those patients, 6 carried mutations in the APC gene. In the analyzed sample, the patients with FAP and the mutant APC gene developed DF at older age (35 years) than the patients with sporadic DF (p = 0.004) and their tumors were not multifocal. This means that sporadic and FAP-associated desmoids have different phenotypes in patients with APC mutations. Patients with sporadic tumors have mutations at the 3'-end of the APC gene more often than individuals with FAP-associated DF. To our knowledge, this is the first study to characterize the subtype of sporadic desmoid fibromatosis phenotypically determined by germline mutations in the APC gene.

scholarly journals Succinate Dehydrogenase B Gene Mutations Predict Survival in Patients with Malignant Pheochromocytomas or Paragangliomas

2007 ◽  
Vol 92 (10) ◽  
pp. 3822-3828 ◽  
Author(s):  
Laurence Amar ◽  
Eric Baudin ◽  
Nelly Burnichon ◽  
Séverine Peyrard ◽  
Stéphane Silvera ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Retrospective Cohort ◽  
Prognostic Value ◽  
Clinical Course ◽  
Malignant Tumors ◽  
Gene Mutations ◽  
Germline Mutations ◽  
Adrenal Tumors ◽  
Probability Of Survival ◽  
Sporadic Tumors

Abstract Context: Pheochromocytomas and paragangliomas may be malignant either at presentation or during recurrence, but the clinical course of malignant tumors is unpredictable. Objective: The objective was to analyze survival according to clinical characteristics at diagnosis of malignancy and the presence or absence of SDHB mutations. Design: This was a retrospective cohort study. Setting and Participants: A total of 54 patients with malignant tumors were included. Malignancy was scored according to the presence of metastases or histologically documented lymph node invasion. Main Outcome Measures: The main outcome was the specific survival after the diagnosis of the first metastasis. Results: Germline mutations were identified in SDHB (n = 23, including 21 patients with apparent sporadic tumors) and VHL (n = 1) genes, and two patients had neurofibromatosis 1. Patients were followed up from the diagnosis of primary tumor and from the diagnosis of the first metastasis to the present or to death with medians of 79 [interquartile range (IQR) 24; 190] and 39 [IQR 14; 94] months, respectively. The 5-yr probability of survival after the diagnosis of the first metastasis was 0.55 (95% confidence interval 0.39–0.69). Patients with SDHB mutations were younger, more frequently had extra-adrenal tumors, and had a shorter metanephrine excretion doubling time. The presence of SDHB mutations was significantly and independently associated with mortality (relative risk 2.7; 95% confidence interval 1.2, 6.4; P = 0.021). Conclusion: SDHB mutations, frequent in patients with malignant pheochromocytomas or paragangliomas, are associated with shorter survival. Therefore, SDHB genetic testing may be of prognostic value for such patients, even those with an apparent sporadic and/or benign presentation at diagnosis.

Clinical and Genetic Characteristics of Phenylketonuria in Ryazan Region

2021 ◽  
Vol 29 (1) ◽  
pp. 5-12
Author(s):  
Grigorii I. Yakubovskii ◽  
Olga B. Serebriakova ◽  
Alina G. Yakubovskaya ◽  
Nadezhda V. Ruban ◽  
Angelina A. Lyakhovets
Keyword(s):  
Blood Level ◽  
Phenylalanine Hydroxylase ◽  
Clinical Course ◽  
Molecular Genetic ◽  
Residual Activity ◽  
Speech Development ◽  
Genetic Characteristics ◽  
Frequent Mutations ◽  
R408w Mutation ◽  
Pah Gene

Aim. This investigation seeks to determine the incidence of phenylketonuria in the Ryazan region, assess the spectrum of mutations in the PAH gene (phenylalanine hydroxylase), investigate the interrelationship between the diseases clinical course, the phenylalanine blood level, and the patients genotype. Materials and Methods. The incidence of phenylketonuria was studied based on the data of massive neonatal screening for the period from 2000 to 2019. Molecular genetic examination of mutations was conducted in 39 patients using the allele-specific multiplex ligation method. The interrelationship between the phenylalanine blood level on the fifth day of life and retest, the diseases clinical course, and the patients genotype was assessed according to the medical record data of 33 patients under dispensary observation in a medico-genetic clinic. The patients were divided into two groups. The first group (n=21) had two severe mutations (residual activity of phenylalanine hydroxylase 10%). The second group (n=12) had one severe and one mild mutation (the residual activity of the enzyme 10%). Results. The incidence of phenylketonuria in the Ryazan region was one in 5054 newborns, exceeding the Russian Federations average parameters. Eighteen mutations were discovered in the PAH gene. The most frequent was the R408W mutation (56.4% alleles). The second most frequent mutations were the IVS10-11GA (6.4%) and P281L (5.1%). The R158Q and Y418C mutations occurred with a frequency of 4.1% and Е280К mutation of 2.7%. All the rest of the mutations occurred as single cases. Investigation of the interrelationship between the phenylalanine blood level, the diseases clinical course, and the patients genotype revealed a reliably higher content of amino acid in the first group on retest (32.11.7 mg/% vs. 17.71.5 mg/% in the second group, р0.001) and predomination of more severe forms of phenylketonuria (90.5% vs. 41.7%, respectively, р0.001). Disorders in neuropsychic and speech development were present in 28.6% of patients in the first group but were absent in the second group. Conclusion. By conducting the study, the incidence of phenylketonuria was determined in the Ryazan region. The spectrum of mutations in the PAH gene was defined. The interrelationship between the diseases clinical portrait, the phenylalanine blood level, and the patients PAH genotype was revealed.

scholarly journals Microsatellite Genetic Markers of Saccharrum spp., and Erianthus sp. on Their Hybrids

2019 ◽  
Vol 3 (1) ◽  
pp. 1
Author(s):  
Mala Murianingrum ◽  
Taryono Taryono ◽  
Rani Agustina Wulandari
Keyword(s):  
Molecular Marker ◽  
Genetic Marker ◽  
Genetic Markers ◽  
Chromosome Segregation ◽  
Molecular Genetic ◽  
Female Parent ◽  
Limiting Factors ◽  
Phenotypic Characteristics ◽  
Saccharum Spp ◽  
Sugarcane Varieties

Progeny identification is the important step that should be done after hybridization. However, polyploidy, aneuploidy and the high chromosome segregation in sugarcane which results various phenotypic characteristics variation and environmental effects become limiting factors to identify the progenies based on morphological characteristic. Microsatellite as one of molecular marker which has codominance inheritance, multiallelic, abundant in the genome and does not influenced by environmental factor is the best tool to asses the crossing fidelity accurately. This research aimed to identify the possibility of genetic marker of Saccharum spp. and Erianthus sp. on their hybrid using microsatellite molecular marker. This study was carried out in Molecular Genetic laboratory, Indonesian Sweetener and Fiber Crops Research Institute (ISFCRI) Malang, from August 2016 to July 2017. Eighty-six (86) F1 intraspecific and interspecific progeny, three commercial sugarcane varieties (PSJT941, PS881 and VMC7616) and two wild types (S. spontaneum dan Erianthus sp.) were assessed genetically by three microsatellite markers. Identification of microsatellite genetic markers was conducted by comparing the visualization band results from electrophoresis of each male and female parent through their progenies. All primers could identify Saccharum spp. and Erianthus sp. genetic markers. There were one to eleven Saccharum spp. and Erianthus sp. genetic markers could be identified such as 2-11 PS881-specific alleles; 2-3 VMC7616-specific alleles; 1-5 PSJT941-specific alleles; two S. spontaneum-specific alleles and 1-2 Erianthus-specific alleles. These findings could be used as the advance genetic marker of microsatellite in sugarcane breeding to asses the cross fidelity.

scholarly journals BT-09 CLINICAL AND MOLECULAR GENETIC FEATURE OF CEREBELLAR GLIOBLASTOMA

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii37-ii38
Author(s):  
Shohei Iijima ◽  
Kuniaki Saito ◽  
Saki Shimizu ◽  
Keiichi Kobayashi ◽  
Daisuke Shimada ◽  
...  
Keyword(s):  
Clinical Course ◽  
Molecular Genetic ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Cerebellar Hemisphere ◽  
Free Survival ◽  
Specific Pcr ◽  
Cerebellar Glioblastoma ◽  
Number Variation ◽  
Dependent Probe

Abstract INTRODUCTION Cerebellar glioblastoma (cGBM) is extremely rare, accounting for 0.7–0.9% of all gliomas. Few studies have reported on clinical course, histopathology, and prognosis. In this report, we discussed cases which were diagnosed as cGBM, and were treated in our institute. Materials and Methods We retrospectively analyzed 9 cGBMs (age ranged 41 to 85 years, median 69), operated at our institute after 2010 January, and evaluated their <MGMT> promoter methylation, <IDH1> mutation, and Copy Number Variation status detected by methylation-specific PCR (MSP), DNA sequencing or immunohistochemistry, and Multiplex Ligation-dependent Probe Amplification (MLPA), respectively. RESULTS All patients underwent resection; 3 gross total resections (GTRs, 33%), 2 subtotal resections, 4 partial resections, with relatively low achievement of GTR. The tumor location predominated in the cerebellar hemisphere (7 patients, 78%) over vermis (2). One patient had brain stem invasion. After surgery, 8 patients received temozolomide (TMZ) and radiotherapy (RT), while did only one RT alone. After recurrence, three patients were treated with bevacizumab monotherapy, and other three received either TMZ and RT, TMZ and ACNU, or TMZ monotherapy. The median progression-free survival (PFS) was 12.0 months, and the median overall survival (OS) was 17.1 months. Five patients (56%) were <MGMT> methylated, whereas all were <IDH1>wild-type. <PTEN> deletion was negative in all patients. <EGFR> amplification and combined <PDGFR> amplification and <CDKN2A> deletion were found in one patient each. DISCUSSION Despite the lower rate of GTR, there was a tendency of longer PFS compared to supratentorial GBM (sGBM). The clinical course after recurrence was unfavorable, and OS thereafter was similar to that of sGBM. cGBMs appeared to lack the typical genetic mutations occurred in sGBM, suggesting that cGBMs might be stimulated with different regulatory cellular signals.

scholarly journals Heterogeneity in Multiple Sclerosis: Comparison of Clinical Manifestations in Relatives

1990 ◽  
Vol 17 (4) ◽  
pp. 387-390 ◽  
Author(s):  
A.D. Sadovnick ◽  
L.L. Hashimoto ◽  
S.A. Hashimoto
Keyword(s):  
Clinical Course ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Initial Symptom ◽  
Study Group ◽  
Disease Course ◽  
Newly Diagnosed ◽  
Lesion Site ◽  
Sibling Pairs ◽  
Index Cases

ABSTRACT:Once diagnosed to have MS, relatives of persons who have been previously diagnosed frequently ask whether their disease course will follow that of their relative(s) with MS. The present study compared the following clinical manifestations of MS among 43 index cases and 47 of their relatives, all of whom were diagnosed to have MS and regularly attended the MS Clinic in Vancouver, British Columbia: (i) age of onset of MS, (ii) clinical course, (iii) lesion site(s) and (iv) initial symptom(s) of MS. The results from the present study are preliminary because of the small size of the study group. However, these data suggest that apart from possibly age of onset between sibling pairs, the clinical manifestations of MS are not correlated among relatives who are assessed according to the same methodology. This is significant for counselling newly diagnosed relatives of longstanding MS patients.

Prevalence and Course of Schizophrenia in a Chinese Rural Area

2003 ◽  
Vol 37 (4) ◽  
pp. 452-457 ◽  
Author(s):  
Mao-Sheng Ran ◽  
Meng-Ze Xiang ◽  
Sheng-Xian Li ◽  
You-He Shan ◽  
Ming-Sheng Huang ◽  
...  
Keyword(s):  
Rural Area ◽  
Clinical Course ◽  
Age Of Onset ◽  
Total Duration ◽  
Community Based ◽  
Factors Affecting ◽  
Total Prevalence ◽  
Duration Of Illness ◽  
Family Economy ◽  
The Status

Objective: To assess the characteristics and factors affecting course of schizophrenia in a Chinese rural area. Method: An epidemiological investigation was conducted to identify all the patients with schizophrenia among 149 231 people in Xinjin County, Chengdu. Results: The total prevalence of schizophrenia was 4.13 per 1000 population. Males had an earlier mean age of onset (29.6 years) than females (32.3 years). Duration of illness before treatment and the total duration of illness were found to be significantly associated with level of remission. The status of treatment, family economy, housing, and families' care of patients had a significant effect on the clinical course of the illness. Conclusions: Duration of illness before treatment may be an important predictor of course in schizophrenia. Early treatment for the patients may produce higher level of improvement in prognosis. Education intervention and community-based service are urgent priorities for these patients.

scholarly journals Clinical and neurophysiologic characterization of an European family with hereditary sensory neuropathy, paroxysmal cough and gastroesophageal reflux

2014 ◽  
Vol 72 (4) ◽  
pp. 269-272 ◽  
Author(s):  
Pedro Barros ◽  
Hugo Morais ◽  
Catarina Santos ◽  
José Roriz ◽  
Paula Coutinho
Keyword(s):  
Gastroesophageal Reflux ◽  
Age Of Onset ◽  
Molecular Genetic ◽  
Genetic Defect ◽  
Sensory Neuropathy ◽  
Dominant Form ◽  
Characteristics Method ◽  
Hereditary Sensory Neuropathy ◽  
Autosomal Dominant Form ◽  
History Of

In 2002, Spring et al reported a family with an autosomal dominant form of hereditary sensory neuropathy; patients also presented adult onset of gastroesophageal reflux and cough. Since then, no further families have been described. Objective: To study a new Portuguese family with these characteristics. Method: To describe the clinical and neurophysiologic characteristics of one family with features of sensory neuropathy associated with cough and gastroesophageal erflux. Results: Three of five siblings presented a similar history of paroxysmal cough (5th decade). About a decade later they experienced numbness and paraesthesia in the feets and in all cases there was evidence of an axonal sensory neuropathy. A history of gastroesophageal reflux of variable severity and age of onset was also present. Discussion: Molecular genetic studies have demonstrated genetic heterogeneity between the hereditary sensory neuropathy type 1 subtypes. The identification of these families is of major importance because further work is required to identify the underlying genetic defect.

scholarly journals Heterozygous APC germline mutations impart predisposition to colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Livia Preisler ◽  
Aline Habib ◽  
Guy Shapira ◽  
Liron Kuznitsov-Yanovsky ◽  
Yoav Mayshar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rna Sequencing ◽  
Disease Severity ◽  
Germline Mutations ◽  
Apc Gene ◽  
Adenomatous Polyposis ◽  
Loss Of Function ◽  
Tumorigenic Transformation ◽  
Hesc Lines ◽  
Apc Mutation

AbstractFamilial adenomatous polyposis (FAP) is an inherited syndrome caused by a heterozygous adenomatous polyposis coli (APC) germline mutation, associated with a profound lifetime risk for colorectal cancer. While it is well accepted that tumorigenic transformation is initiated following acquisition of a second mutation and loss of function of the APC gene, the role of heterozygous APC mutation in this process is yet to be discovered. This work aimed to explore whether a heterozygous APC mutation induces molecular defects underlying tumorigenic transformation and how different APC germline mutations predict disease severity. Three FAP-human embryonic stem cell lines (FAP1/2/3-hESC lines) carrying germline mutations at different locations of the APC gene, and two control hESC lines free of the APC mutation, were differentiated into colon organoids and analyzed by immunohistochemistry and RNA sequencing. In addition, data regarding the genotype and clinical phenotype of the embryo donor parents were collected from medical records. FAP-hESCs carrying a complete loss-of-function of a single APC allele (FAP3) generated complex and molecularly mature colon organoids, which were similar to controls. In contrast, FAP-hESCs carrying APC truncation mutations (FAP1 and FAP2) generated only few cyst-like structures and cell aggregates of various shape, occasionally with luminal parts, which aligned with their failure to upregulate critical differentiation genes early in the process, as shown by RNA sequencing. Abnormal disease phenotype was shown also in non-pathological colon of FAP patients by the randomly distribution of proliferating cells throughout the crypts, compared to their focused localization in the lower part of the crypt in healthy/non-FAP patients. Genotype/phenotype analysis revealed correlations between the colon organoid maturation potential and FAP severity in the carrier parents. In conclusion, this study suggest that a single truncated APC allele is sufficient to initiate early molecular tumorigenic activity. In addition, the results hint that patient-specific hESC-derived colon organoids can probably predict disease severity among FAP patients.

Characters of germline mutations in Chinese non-small cell lung cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13542-e13542
Author(s):  
Yuan Qiu ◽  
Liping Liu ◽  
Qiuhua Deng ◽  
Haihong Yang ◽  
Hanzhang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Age Of Onset ◽  
Statistical Significance ◽  
Susceptibility Gene ◽  
Germline Mutations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e13542 Background: Environment factors are associated with lung cancer occurrence. Genetic susceptibility to lung cancer remains unclear. This study assessed germline mutations in Chinese non-small-cell lung cancer (NSCLC) patients. Methods: 506 FFPE samples were collected from 469 patients pathologically confirmed as lung adenocarcinoma. A 508-gene panel including 63 hereditary cancer genes was applied to detect mutations on MGI-seq 2000. Raw data was processed and analyzed. Variation pathogenicity was categorized following ACMG 2015 guideline. Results: 21 patients (4%) carried (likely) pathogenic (P or LP) mutations in 15 cancer predisposition genes. 11 germline variations included MUTYH (1/21), BLM (1/21), BRIP1(2/21), RAD50(1/21), PMS1(1/21), TP53(1/21), BRCA2(1/2), PALB2(1/21), NF1(1/21), CDH1(1/21) and MRE11A (1/21) genes. Nine likely pathogenic mutations were identified in MRE11A, RAD51C, RAD50, ATR, BRCA2, BLM, PMS1 and VHL genes. These mutations are involved in homologous recombination repair, mismatch repair, Fanconi anemia, and Li-Fraumeni syndrome. Germline mutations were commonly occurred in females (female vs Male: 13 vs 7) without statistical significance. No significant correlations of age of onset and TMB were observed between NSCLC patients with germline wild type and mutation. Other clinical characters like histology and clinical stage presented similar results. Somatic mutations with high frequency like EGFR, KRAS were distributed equally in patients with both germline mutation positive and negative. Conclusions: In this study, there is no significant correlation of germline susceptibility gene mutations with clinical and genetic characters of NSCLC patients. Further investigation on germline genetic aberrations of NSCLC is definitely needed to clarify germline impact on the etiology of NSCLC. [Table: see text]

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