scholarly journals The case of multiple osteohondromas in Yakut family (Eastern Siberia, Russia) caused by rare mutation in the EXT2 gene

2019 ◽  
pp. 25-33
Author(s):  
А.Е. Яковлева ◽  
Д.А. Петухова ◽  
П.И. Голикова ◽  
Е.Е. Гуринова ◽  
А.Л. Данилова ◽  
...  
Keyword(s):  
In Silico ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Molecular Genetic ◽  
In Silico Analysis ◽  
Molecular Genetic Analysis ◽  
Molecular Genetic Study ◽  
Rare Mutation ◽  
Skeletal Disease ◽  
Multiple Cartilaginous Exostoses

Введение. Множественная экзостозная хондродисплазия (МЭХД) - наследственное аутосомно-доминантное заболевание скелета, которое характеризуется образованием множественных хрящевых экзостозов в зонах роста костей. Консультирование семей с МЭХД является сложной задачей для врача-генетика. В статье приведены клинические, молекулярно-генетические данные обследования большой якутской семьи с аутосомно-доминантной наследственной МЭХД, причиной которой является редкая мутация в гене EXT2. Цель: проведение клинико-генеалогического, молекулярно-генетического обследования больных с клиническим диагнозом МЭХД. Методы. В исследование включены 4 поколения одной якутской семьи (11 больных и здоровых членов). Секвенирование экзома одного члена семьи (ДНК пробанда) проводилось на секвенаторе MiSeq Illumina с использованием панели, включающей 4800 генов. Патогенность выявленной мутации подтверждалась in silico, а также секвенированием по Сэнгеру с использованием ДНК пробанда, его родителей. Данный метод также был использован для выявления мутации у остальных членов семьи. Результаты. В результате молекулярно-генетического исследования у 7 членов семьи с клиническим диагнозом МЭХД была выявлена редкая нонсенс-мутация c.751С>T в экзоне 5 гена EXT2 в гетерозиготном состоянии. Данная мутация отсутствовала у 4 здоровых членов этой семьи, а также в 10 образцах из контрольной группы. Оценка патогенности выявленной мутации показала, что данная мутация является причиной возникновения МЭХД в якутской семье. Заключение. Ранняя медицинская помощь пациентам с диагнозом МЭХД может дать возможность оказания медицинской помощи пациентам специалистами разного профиля, а также сосредоточить внимание врачей на ортопедических проблемах в раннем возрасте. Introduction. Multiple osteohondromas (MO) is an autosomal dominant inherited skeletal disease characterized by the formation of multiple cartilaginous exostoses in the areas of growth in a long bones. Difficult issues arise for the genetic counseling of families with MO. We presents the clinical and molecular genetic analysis of four-generation Yakut family with an autosomal dominant inherited MO, caused by a rare mutation in the EXT2 gene. Aim: сonducting a clinical, genealogical, molecular genetic study of patients with a clinical diagnosis MO. Methods. Targeted panel sequencing performed for the 4800 known candidate genes using Trusight One Sequencing Panel (Illumina Inc., USA) on one sample (DNA of proband). Sanger sequencing was performed for validation of candidate disease causing mutation in DNA from a proband and family members. Results. A rare EXT2 nonsense mutation (c.751C> T, p.Gln251*) was revealed by targeted exome sequencing and validated by Sanger sequencing in the 7 MO-affected members of this family. The variant was interpreted as pathogenic based on an in silico analysis. This mutation was absent in 4 healthy members of this family and in 10 controls. Conclusions. This is the first study of EXT2 gene mutation in a Russian patients from Yakut family with MO. Timely health care of patients with diagnosis of MO can contribute to establishment coordinated multispecialty management of the patient focusing on the orthopedic problems issues through childhood.

scholarly journals Molecular genetic analysis of the EXT2 gene - causes of hereditary multiple exostoses in Yakuts

2020 ◽  
pp. 59-60
Author(s):  
А.Е. Яковлева ◽  
Д.А. Петухова ◽  
А.Л. Данилова ◽  
А.Л. Сухомясова ◽  
Н.Р. Максимова
Keyword(s):  
Genetic Analysis ◽  
Clinical Diagnosis ◽  
Sanger Sequencing ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Genetic Studies ◽  
Rare Mutation ◽  
Parallel Sequencing ◽  
Hereditary Multiple Exostoses ◽  
Multiple Exostoses

В статье представлены результаты молекулярно-генетических исследованиий больных с множественной экзостозной хондродисплазией (МЭХД), причиной которой явилась редкая мутация в гене EXT2. Исследованы 65 больных с МЭХД и их родственников из 30 неродственных семей. Для молекулярно-генетического анализа было использовано массовое параллельное секвенирование и прямое секвенирование по Сэнгеру. У 16 больных из 4 семей с клиническим диагнозом МЭХД была выявлена редкая нонсенс-мутация c.751С>T в экзоне 5 гена EXT2 в гетерозиготном состоянии. Here we present molecular genetic studies of Yakut patients with hereditary multiple exostoses (HME), which caused by a rare mutation in the EXT2 gene. A total of 65 patients with clinical diagnosis of HME and their relatives from 30 unrelated families were examined. For molecular genetic analysis, massive parallel sequencing (MPS) and direct Sanger sequencing were used. In 16 patients from 4 families with a clinical diagnosis of HME, a rare heterozygous nonsense mutation c.751C> T was detected in exon 5 of the EXT2.

scholarly journals Genotyping Fanconi anemia patients from Serbia reveals three novel FANCD2 variants

Genetika ◽  
2017 ◽  
Vol 49 (2) ◽  
pp. 559-572
Author(s):  
Jelena Filipovic-Trickovic ◽  
Vesna Mandusic ◽  
Ivana Joksic ◽  
Dragana Vujic ◽  
Ana Valenta-Sobot ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
In Silico ◽  
Wide Spectrum ◽  
Molecular Genetic ◽  
In Silico Analysis ◽  
Molecular Genetic Analysis ◽  
Sequence Variants ◽  
Inherited Disease ◽  
Progressive Pancytopenia ◽  
Silico Analysis

Fanconi anemia is rare inherited disease characterized by wide spectrum of congenital anomalies, progressive pancytopenia, and predisposition to hematological malignancies and solid tumors. Molecular genetic analysis of mutations in FANC genes is of a great importance for diagnosis confirmation, prenatal and carrier testing, as well as for prediction of chemotherapy outcome and disease complications. In this study we performed screening of frequently affected regions of FANCD2 gene for sequence variants in six unrelated FA-D2 patients in Serbia. This is the first molecular analysis of FANCD2 gene in Serbian FA-D2 patients. A total of 10 sequence variants were detected, one in homozygous, and nine in heterozygous state. Two variants were found within exons, and eight within introns, in deep intronic regions. In-silico analysis showed that among all detected variants one exon variant and three intron variants might have impact on splicing mechanism. Heterozygous variants found in intron 3, c.206-246delG; exon 26, c.2396 C>A and intron 28, c.2715+573 C>T were not previously reported. In-silico analysis revealed that among them, two (intron 3, c.206-246 delG and exon 26, c.2396 C>A) could be novel disease-causing mutations. Many variants were found in more than one patient, including those unreported, indicating their possible ethnic association. Great number of variants in some patients suggests their non-random emergence in Fanconi anemia pathway.

scholarly journals Molecular Genetic Analysis of RB1 gene among Sudanese children with Retinoblastoma

2019 ◽  
Author(s):  
Nada O. Ibrahim ◽  
Mahgoub Saleem ◽  
Entesar Eltayeb ◽  
Salwa Mekki ◽  
Elteleb G. Elnaim ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Genetic Analysis ◽  
In Silico ◽  
Molecular Genetic ◽  
Geographical Area ◽  
Good Prognosis ◽  
Molecular Genetic Analysis ◽  
Molecular Genetic Study ◽  
Genetic Sequencing ◽  
Life Threatening

BACKGROUNDRetinoblastoma (RB), the commonest early childhood intraocular tumor, is most often related to mutations in the RB1 gene with an incidence of 3% of all pediatric tumors. It has good prognosis if diagnosed early but it is life-threatening when diagnosed late.OBJECTIVETo study the Molecular Genetic Analysis of Retinoblastoma (RB) in Sudanese families.METHODSThirty one (n=31) clinically and histopathologically diagnosed cases of RB attending Makkah Eye Complex (MEC) Orbit clinic (Khartoum, Sudan) were included in this Molecular Genetic RB Analysis. Fresh blood samples extracted from seven RB patients and 15 close families for DNA extraction and PCR were sent for Genetic Sequencing and In silico approach for “Exon 18 mutations” which is one of the highly mutated exons worldwide.RESULTSThe majority of patients (41.9%) were below five years old. Females were 58.1%, males were 41.9%. Leukocoria was the commonest sign at presentation (41.9%). RB Unilaterality were in (77.4%) while Bilaterality in 19.4%. Both eyes were equally affected 50% each. The age at diagnosis time ranged from 0.02 to five years. Consanguinity of parents was very high (85.7%), the 1st degree cousins were less (28.6%) while the 2nd degree was high (57.1%). The patients’ ethnic background and geographical area were from seven different tribes; all belong to the Western Sudan. The molecular genetic study showed that exon 18 was free of mutation among the seven patients + their three relatives. The Functional Analysis and (SNPs) prediction study of exon 18 from NCBI data base showed that the various computational approaches used (SIFT, PolyPhen-2, I-mutant and Project hope) identified 16 reported mutations worldwide, three of which (rs137853292, rs375645171 and rs772068738) are major nsSNPs (non-synonymous) which might contribute to native RB1 protein malfunction and ultimately causing carcinoma.CONCLUSIONRB mainly affected children under five years and both sexes are equally affected. Unilaterality was predominant. Consanguinity plays a role in inheritance and the majority of patients were from Western Sudan. The most commonly detected deleterious mutations worldwide in exon 18 were not found in the Sudanese studies samples. Further screening for the highly reported mutations in exons 8, 10 and 14 or Next Generation Sequencing (NGS) are recommended. In silico tools are useful in studying the functional analysis of SNPs.

A novel CRYBB2 mutation causes autosomal dominant cataract: A report from a Chinese family

2020 ◽  
pp. 112067212092645
Author(s):  
Li Juan Xu ◽  
Zhi Gang Lv ◽  
Ying Liu ◽  
Xiang Xiang Zhang ◽  
Yu Xin Cui ◽  
...  
Keyword(s):  
Axial Length ◽  
Healthy Subjects ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Pathogenic Mutation ◽  
Chinese Family ◽  
Rare Mutation ◽  
Pathogenic Variants ◽  
Lens Opacities ◽  
Generation Sequencing

Purpose This study aimed to examine pathogenic mutation within one Chinese family of five-generations suffering from autosomal dominant cataract. Methods Next-generation sequencing and Sanger sequencing were used to find the pathogenic variants. Results A rare mutation, c.563G > A, in CRYBB2 gene was found in the proband that showed symptom of non-syndromic congenital autosomal dominant cataract. This mutation had been found in all affected individuals and in one healthy infant, but it did not exist between two individuals who did not develop such disease in that family, as well as in 100 healthy subjects who showed no relation with that family. Cataracts in this family varied with different severity of lens opacities and elongation of axial length. Conclusion One missense mutation c.563G > A is reported in the CRYBB2 gene among one Chinese family suffering from early-onset cataract, and associated novel phenotypes are the elongation of axial length and the types of cataract. Our results expand the spectrum of associated phenotypes of CRYBB2 mutation.

scholarly journals In silico analysis of CDC73 gene revealing 11 novel SNPs associated with Jaw Tumor Syndrome

2019 ◽  
Author(s):  
Abdelrahman H. Abdelmoneim ◽  
Alaa I. Mohammed ◽  
Esraa O. Gadim ◽  
Mayada A.Mohammed ◽  
Sara H. Hamza ◽  
...  
Keyword(s):  
In Silico ◽  
Autosomal Dominant ◽  
In Silico Analysis ◽  
Autosomal Dominant Disorder ◽  
Variable Expression ◽  
Back Ground ◽  
And Function ◽  
Molecular Aberrations ◽  
The Impact ◽  
Silico Analysis

AbstractBack groundhyperparathyroidism-jaw tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the effect of SNPs on CDC73 structure and function using different bioinformatics tools.MethodComputational analysis using eight different in-silico tools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, PMut and Imutant were used to identify the impact on the structure and/or function of CDC73 gene that might be causing jaw tumour.ResultsFrom (733) SNPs identified in the CDC73 gene we found that only Eleven were deleterious to the function and structure of protein and expected to cause syndrome.ConclusionEleven substantial genetic/molecular aberrations in CDC73 gene were identified that could serve as actionable targets for chemotherapeutic intervention in patients whose disease is no longer surgically curable.

scholarly journals Molecular genetic analysis of the strain Leningrad-16 used for the production of measles vaccine

2020 ◽  
Vol 97 (2) ◽  
pp. 182-189
Author(s):  
Georgy M. Ignatyev ◽  
Alena V. Atrasheuskaya ◽  
Lidiya L. Sukhanova ◽  
Elena S. Sidorenko ◽  
Nina A. Netesova
Keyword(s):  
Vaccine Strain ◽  
Measles Virus ◽  
Restriction Analysis ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Rt Pcr ◽  
Virus Genotype ◽  
Molecular Genetic Study ◽  
Production Stages ◽  
Pcr Method

Aim. To study the genetic stability of the measles virus strain Leningrad-16 (L-16) used for the production of vaccine at JSC NPO Mikrogen.Materials and methods. A series of production and sowing strains of L-16 (JSC NPO Mikrogen), ready-made series of measles vaccines from various manufacturers, and the strain of measles virus genotype D6 were studied. Molecular genetic study of the strains was performed using RT-PCR followed by restriction analysis and sequencing.Results. The complete genome sequences of the production and sowing strains of L-16 that are used for vaccine production were obtained. The sequence of the vaccine strain was deposited in GenBank. Strain L-16 was confirmed to be genetically stable. The obtained data demonstrated the possibility of using the RT-PCR method with subsequent restriction analysis to confirm the authenticity of the vaccine strain L-16 in finished mono and three component vaccines.Conclusion. The results of the study suggest the applicability of the molecular genetic methods to confirm the authenticity of the studied strains not only at the production stages, but also in the finished series of vaccines.

scholarly journals Molecular-genetic characterization of the human non-hypervariable GC-rich minisatellite UPS29 of gene CENTB5

2007 ◽  
Vol 5 (3) ◽  
pp. 35-45 ◽  
Author(s):  
Irina O Suchkova ◽  
Daria M Shubina ◽  
Ludmila K Sasina ◽  
Natalia O Slominska ◽  
Vadim B Vasilyev ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
In Silico ◽  
Genetic Characterization ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
First Time ◽  
Molecular Genetic Characterization

Human minisatellite UPS29 localized in one of CENTB5 introns was studied in silico and using molecular genetic analysis. For the first time there were revealed seven UPS29 alleles which contained 6-24 repeated units. Allele consisting of 17 repeats was prevailed (91,5 %). Frequency of other alleles varied from 0,29 % to 4,39 %. UPS29 heterozygosity was 12,3 %. Minisatellite UPS29 was classified as low polymorphic and non hypervariable.

scholarly journals Genetic analysis of the STIM1 gene in chronic pancreatitis

2019 ◽  
Author(s):  
Emmanuelle Masson ◽  
Wen-Bin Zou ◽  
Claudia Ruffert ◽  
Vanessa Holste ◽  
Patrick Michl ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Genetic Analysis ◽  
Sanger Sequencing ◽  
Complex Disease ◽  
Molecular Genetic ◽  
Acinar Cells ◽  
Molecular Genetic Analysis ◽  
Chinese Patients ◽  
Pancreatic Acinar Cells ◽  
Coding Variants

ABSTRACTChronic pancreatitis is a complex disease that involves many factors, both genetic and environmental. Over the past two decades, molecular genetic analysis of five genes that are highly expressed in human pancreatic acinar cells, namely PRSS1, PRSS2, SPINK1, CTRC and CTRB1/CTRB2, has established that a trypsin-dependent pathway plays a key role in the etiology of chronic pancreatitis. Since Ca2+ deregulation can lead to intracellular trypsin activation in experimental acute pancreatitis, we analyzed STIM1 (encoding stromal interaction molecule-1, the main regulator of Ca2+ homeostasis in pancreatic acinar cells) as a candidate modifier gene in French, German and Chinese patients with chronic pancreatitis. The French and German subjects were analyzed by Sanger sequencing whereas the Chinese subjects were analyzed by targeted next-generation sequencing confirmed by Sanger sequencing. A total of 37 rare coding variants (35 missense and 2 nonsense) were identified, which were enriched in patients as compared with controls [2.28% (47/2,057) vs. 0.99% (33/3,322); odds ratio = 2.33, P = 0.0001]. This is the first large case-control study to demonstrate a putative association of rare STIM1 coding variants with chronic pancreatitis. Functional analysis will be required to clarify whether or not the rare STIM1 variants detected predispose to pancreatitis.

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