scholarly journals Clinical and genetic characteristics of ponto-cerebellar hypoplasia caused by mutations in the TSEN54 gene (OMIM: 277470)

2019 ◽  
Vol 9 (2) ◽  
pp. 30-36
Author(s):  
E. I. Dadali ◽  
I. A. Akimova ◽  
N. A. Semenova ◽  
D. M. Guseva ◽  
O. A. Shchagina ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Compound Heterozygous ◽  
Pontocerebellar Hypoplasia ◽  
Genetic Characteristics ◽  
Molecular Genetic Diagnosis ◽  
Severity Of The Disease ◽  
Detection Of Mutations ◽  
Compound Heterozygous State

Introduction. The description of the clinical and genetic characteristics of eight patients with autosomal-recessive variant pontocerebellar hypoplasia due to mutations in the TSEN54 gene.Purpose. Description of clinical and genetic characteristics of Russian patients with type 2A and type 4 of pontocerebellar hypoplasia.Materials and methods. The diagnosis of pontocerebellar hypoplasia was established on the basis of the specific features of clinical manifestations and detection of mutations in the gene TSEN54 based on the analysis of the results of exome sequencing. Results. 8 patients with pontocerebellar hypoplasia caused by mutations in the TSEN54 gene were identified. Discussion. Based on the features of clinical manifestations and severity of the disease in 5 patients diagnosed pontocerebellar hypoplasia type 2A, and in 3 patients – type 4. In patients with type 2A of pontocerebellar hypoplasia discovered mutation c. 919G>T (p.Ala307Ser)  in a homozygous state. Patients with type 4 of pontocerebellar hypoplasia this mutation is detected in the compound heterozygous state with c.670_671delAA (p.Lys224fs) and c.1264C>T (p.Gln422fs).Conclusion. The obtained results allow us to conclude that, as well as in European populations, the mutation c.919G>T (p. Ala307Ser) is a major in Russian patients with pontocerebellar hypoplasia 2A and 4 types, which account for about half of all cases of this disease group. The search for this mutation should be the first stage of molecular genetic diagnosis in patients with clinical and magnetic resonance signs of pontocerebellar hypoplasia.

Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism

2020 ◽  
Vol 33 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tatsushi Tanaka ◽  
Kohei Aoyama ◽  
Atsushi Suzuki ◽  
Shinji Saitoh ◽  
Haruo Mizuno
Keyword(s):  
Congenital Hypothyroidism ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Japanese Patients ◽  
Thyroid Stimulating Hormone ◽  
Allelic Variant ◽  
Genetic Investigation ◽  
Pathogenic Variants ◽  
Recessive Genes ◽  
Molecular Genetic Diagnosis

AbstractObjectivesCongenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.MethodsWe enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.ResultsWe identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants.ConclusionsThe prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.

Mitochondrial encephalopathies: molecular genetic diagnosis from blood samples

The Lancet ◽  
1991 ◽  
Vol 337 (8753) ◽  
pp. 1311-1313 ◽  
Author(s):  
S.R. Hammans ◽  
M.G. Sweeney ◽  
M. Brockington ◽  
J.A. Morgan-Hughes ◽  
A.E. Harding
Keyword(s):  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Blood Samples ◽  
Molecular Genetic Diagnosis

Clinical and genetic characteristics of rare pathogenic variants of the CFTR gene in Russian patients with cystic fibrosis

2021 ◽  
Vol 31 (2) ◽  
pp. 148-158
Author(s):  
A. Yu. Voronkova ◽  
Yu. L. Melyanovskaya ◽  
N. V. Petrova ◽  
T. A. Adyan ◽  
E. K. Zhekaite ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Variants ◽  
Pancreatic Insufficiency ◽  
Protein Energy Malnutrition ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Cftr Gene ◽  
Genetic Characteristics ◽  
Missense Variants ◽  
Pathogenic Variants

The variety of clinical manifestations of cystic fibrosis is driven by the diversity of the CFTR gene nucleotide sequence. Descriptions of the clinical manifestations in patients with the newly identified genetic variants are of particular interest.The aim of this study was to describe clinical manifestations of the disease with the newly identified genetic variants.Methods. Data from Registry of patients with cystic fibrosis in the Russian Federation (2018) were used. The data review included three steps — the search for frequent mutations, Sanger sequencing, and the search for extensive rearrangements by MLPA. 38 pathogenic variants were identified that were not previously described in the international CFTR2 database. We selected and analyzed full case histories of 15 patients with 10 of those 38 pathogenic variants: p.Tyr84*, G1047S, 3321delG, c.583delC, CFTRdele13,14del18, CFTRdele19-22, c.2619+1G>A, c.743+2T>A, p.Glu1433Gly, and CFTRdel4-8del10-11.Results. A nonsense variant p.Tyr84* was found in 5 patients (0.08 %). Two missense variants c.3139G>A were found in 2 siblings (0.03 %). The c.4298A>G was found in 1 patient. Other variants were detected in a single patient (0.02 %) each. They included two variants of a deletion with a shift of the reading frame 3321delG and c.583delC, two splicing disorders c.2619+1G>A and c.743+2T>A, three extended rearrangements CFTRdele19-22, CFTRdele13,14del18, and CFTRdel4-8del10-11. The last two variants include 2 rearrangements on one allele, which cause the severe course in two young children. 8 of the 10 variants are accompanied by pancreatic insufficiency (PI). Among patients with p.Tyr84*, one had ABPA, one had liver transplantation, and all had Pseudomonas aeruginosa infection. Nasal polyps were diagnosed in 2 patients with p.Tyr84*, 1 with G1047S, 1 with CFTRdel4-8del10-11, and 1 patient with 3321delG, who also had osteoporosis and cystic fibrosis-related diabetes (CFRD). 2 patients with PI with 3321delG and CFTRdel4-8del10-11 genetic variants, and 1 with PI with p.Glu1433Gly genetic variant had severe protein-energy malnutrition (PEM).Conclusion. Clinical manifestations of previously undescribed CFTR genetic variants were described. 5/10 genetic variants should be attributed to class I, 3/10 – to class 7 of the function classification of pathogenic CFTR gene variants associated with transcription and translation disruptions. Class of the identified missense variants c.3139G>A and c.4298A>G has not been established and requires further functional, cultural, and molecular genetic studies.

scholarly journals Clinician's modern approaches to molecular genetic diagnosis of glioblastomas

2021 ◽  
Vol 67 (1) ◽  
pp. 13-19
Author(s):  
Turna Ashkhatcava ◽  
Marina Tatarinova ◽  
Lali Kogoniya ◽  
David Naskhletashvili ◽  
Vadim Zhukov
Keyword(s):  
Braf Mutation ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Braf V600e ◽  
Poor Prognostic Factor ◽  
Molecular Genetic Diagnosis ◽  
The Brain ◽  
Tert Mutation ◽  
Primary Glioblastomas

The article is devoted to the issue of molecular genetic diagnosis of cerebral glioblastomas. Despite significant advances in neurooncology, little progress has been made in prolonging the life of patients with cerebral glioblastoma, and a significant part of the effectiveness of treatment depends on the recognition of two prognostic biomarkers: mutations of the isocitrate dehydrogenase (IDH) promoter and  the methylation of the O6-methylguanine methyl transferase (MGMT) promoter. The article summarizes the data of world and domestic clinical studies, allowing to supplement the histological characteristics of primary glioblastomas with genetic markers: the presence of the TERT mutation, EFGR amplification, loss of PTEN function, LOH 10q, and the presence of the BRAF mutation. It should be noted that the amplification of EGFR, causing resistance to apoptotic stimuli and alkylating chemotherapy with Temozolomide, attracts much attention as a therapeutic target. The frequency of occurrence of the TERT mutation is 90% of all tumors of various genesis, most often the TERT mutation is found in oligodendroglioma or primary glioblastoma. Loss of heterozygosity in the region of localization of the PTEN gene is observed in many types of sporadic tumors, including more than 40% of glioblastomas. Mutations in this gene are found in tumors of the brain, endometrium, prostate, kidney, and mammary gland. The presence of a PTEN mutation is a poor prognostic factor. LOH 22q is much more common in secondary glioblastomas (82%) than in primary glioblastomas (41%). Among brain tumors, the BRAF mutation is most common with pleomorphic xanastrocytoma (60-70%).The BRAF V600E mutation was found in epithelioid glioblastoma, which is a rare and aggressive type of glioblastoma, characterized by an unfavorable prognosis (about 6 months) and frequent leptomeningeal spread. Thus, knowledge of the molecular mechanisms of carcinogenesis will enable a personalized approach to treatment with glioblastomas of the brain.

scholarly journals Molecular Genetic Diagnosis of von Hippel-Lindau Disease: Analysis of Five Japanese Families

1996 ◽  
Vol 87 (5) ◽  
pp. 423-428 ◽  
Author(s):  
Hiroshi Kanno ◽  
Taro Shuin ◽  
Keiichi Kondo ◽  
Susumu Ito ◽  
Masahiko Hosaka ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Molecular Genetic Diagnosis ◽  
Disease Analysis
Sign in / Sign up

Export Citation Format

Share Document