scholarly journals Targeted genomic enrichment and massively parallel sequencing identifies novel nonsyndromic hearing impairment pathogenic variants in Cameroonian families

2016 ◽  
Vol 90 (3) ◽  
pp. 288-290 ◽  
Author(s):  
K. Lebeko ◽  
C. M. Sloan-Heggen ◽  
J. J. N. Noubiap ◽  
C. Dandara ◽  
D. L. Kolbe ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
Massively Parallel Sequencing ◽  
Massively Parallel ◽  
Parallel Sequencing ◽  
Pathogenic Variants ◽  
Targeted Genomic Enrichment

scholarly journals Genetic diagnosis of congenital hypopituitarism by a target gene panel: novel pathogenic variants in GLI2, OTX2 and GHRHR

2019 ◽  
Vol 8 (5) ◽  
pp. 590-595 ◽  
Author(s):  
Marilena Nakaguma ◽  
Fernanda A Correa ◽  
Lucas S Santana ◽  
Anna F F Benedetti ◽  
Ricardo V Perez ◽  
...  
Keyword(s):  
Target Gene ◽  
Gh Deficiency ◽  
Massively Parallel Sequencing ◽  
Genetic Diagnosis ◽  
Pituitary Hormones ◽  
Gene Panel ◽  
Massively Parallel ◽  
Parallel Sequencing ◽  
Pathogenic Variants ◽  
Congenital Hypopituitarism

Aim Congenital hypopituitarism has an incidence of 1:3500–10,000 births and is defined by the impaired production of pituitary hormones. Early diagnosis has an impact on management and genetic counselling. The clinical and genetic heterogeneity of hypopituitarism poses difficulties to select the order of genes to analyse. The objective of our study is to screen hypopituitarism genes (candidate and previously related genes) simultaneously using a target gene panel in patients with congenital hypopituitarism. Methods Screening of 117 subjects with congenital hypopituitarism for pathogenic variants in 26 genes associated with congenital hypopituitarism by massively parallel sequencing using a customized target gene panel. Results We found three novel pathogenic variants in OTX2 c.295C>T:p.Gln99*, GLI2 c.1681G>T:p.Glu561* and GHRHR c.820_821insC:p.Asp274Alafs*113, and the previously reported variants in GHRHR c.57+1G>A and PROP1 [c.301_302delAG];[c.109+1G>A]. Conclusions Our results indicate that a custom-designed panel is an efficient method to screen simultaneously variants of biological and clinical relevance for congenital GH deficiency. A genetic diagnosis was possible in 5 out of 117 (4%) patients of our cohort. We identified three novel pathogenic variants in GHRHR, OTX2 and GLI2 expanding the spectrum of variants associated with congenital hypopituitarism.

scholarly journals ATP7B gene study using massively parallel sequencing in patients with Wilson's disease

2020 ◽  
pp. 97-98
Author(s):  
Н.А. Скрябин ◽  
О.Ю. Васильева ◽  
А.А. Сивцев ◽  
И.Ж. Жалсанова ◽  
А.Е. Постригань ◽  
...  
Keyword(s):  
Wilson’S Disease ◽  
Massively Parallel Sequencing ◽  
Wilson's Disease ◽  
Massively Parallel ◽  
Atp7b Gene ◽  
Parallel Sequencing ◽  
Pathogenic Variants ◽  
Efficient Detection ◽  
Gene Study ◽  
Detection Of Mutations

Болезнь Вильсона-Коновалова (БВК) - аутосомно-рецессивное заболевание, развивающееся вследствие накопления меди в организме при повреждениях гена АТР7В. В настоящем исследовании проводился поиск мутаций в этом гене методом массового параллельного секвенирования у больных с БВК. Для целевого обогащения интересуемых регионов была разработана панель праймеров для ПЦР длинных фрагментов. У 6 пациентов из 12 проанализированных выявлены патогенные и вероятно патогенные варианты нуклеотидной последовательности гена АТР7В. Полученные результаты указывают на то, что разработанный метод таргетного массового параллельного секвенирования позволяет эффективно выявлять мутации в гене ATP7B. Wilson’s disease is an autosomal recessive disease that develops as a result of the accumulation of copper in the organism when the ATP7B gene is damaged. The present study searched for mutations in this gene using massively parallel sequencing in patients with Wilson’s disease. For targeted enrichment of the regions of interest, a primer panel for PCR of long fragments was developed. In 6 patients out of 12 analyzed, pathogenic and probably pathogenic variants of the nucleotide sequence of the ATP7B gene were identified. The obtained results indicate that the developed method of targeted massively parallel sequencing allows efficient detection of mutations in the ATP7B gene.

Brief Report of Variants Detected in Hereditary Hearing Loss Cases in Iran over a 3-Year Period

2020 ◽  
Author(s):  
Niloofar BAZAZZADEGAN ◽  
Raheleh VAZEHAN ◽  
Mahsa FADAEE ◽  
Zohreh FATTAHI ◽  
Ayda ABOLHASSANI ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Genetic Testing ◽  
Massively Parallel Sequencing ◽  
Cost Effective ◽  
Massively Parallel ◽  
Parallel Sequencing ◽  
Hereditary Hearing Loss ◽  
Targeted Genomic Enrichment ◽  
Novel Variants ◽  
Autosomal Recessive Pattern

Background: Diagnosis of hereditary hearing loss (HHL) as a heterogeneous disorder is very important especially in countries with high rates of consanguinity where the autosomal recessive pattern of inheritance is prevalent. Techniques such as next-generation sequencing, a comprehensive genetic test using targeted genomic enrichment and massively parallel sequencing (TGE + MPS), have made the diagnosis more cost-effective. The aim of this study was to determine HHL variants with comprehensive genetic testing in our country. of this study was to determine HHL variants with comprehensive genetic testing in our country. Methods: Fifty GJB2 negative individuals with HHL were referred to the Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, one of the reference diagnostic genetic laboratories in Iran, during a 3-year period between 2014 and 2017. They were screened with the OtoSCOPE test, the targeted genomic enrichment and massively parallel sequencing (TGE + MPS) platform after a detailed history had been taken along with clinical evaluation. Results: Among 32 out of 50 GJB2 negative patients (64%), 34 known pathogenic and novel variants were detected of which 16 (47%) were novel, identified in 10 genes of which the most prevalent were CDH23, MYO7A and MYO15A. Conclusion: These results provide a foundation from which to make appropriate recommendations for the use of comprehensive genetic testing in the evaluation of Iranian patients with hereditary hearing loss.

Novel Mutations in GRXCR1 at DFNB25 Lead to Progressive Hearing Loss and Dizziness

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 129S-134S ◽  
Author(s):  
Kentaro Mori ◽  
Ikuyo Miyanohara ◽  
Hideaki Moteki ◽  
Shin-ya Nishio ◽  
Yuichi Kurono ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Massively Parallel Sequencing ◽  
Massively Parallel ◽  
Compound Heterozygous ◽  
Nonsyndromic Hearing Loss ◽  
Novel Mutations ◽  
Progressive Hearing Loss ◽  
Severe Hearing Loss ◽  
Parallel Sequencing ◽  
Targeted Genomic Enrichment

Objective: We identified 2 patients in 1 family who had novel mutations in GRXCR1, which caused progressive hearing loss. Methods: One thousand one hundred twenty Japanese hearing loss patients with sensorineural hearing loss from unrelated families were enrolled in this study. Targeted genomic enrichment with massively parallel sequencing of all known nonsyndromic hearing loss genes was used to identify the genetic causes of hearing loss. Results: In this study, 2 affected individuals with compound heterozygous mutations—c.439C>T (p.R147C) and c.784C>T (p.R262X)—in GRXCR1 were identified. The proband had moderate to severe hearing loss and suffered from dizziness with bilateral canal paralysis. Conclusion: Our cases are the first identified in the Japanese population and are consistent with previously reported cases. The frequency of mutations in GRXCR1 seems to be extremely rare. This study underscores the importance of using comprehensive genetic testing for hearing loss. Furthermore, longitudinal audiologic assessment and precise vestibular testing are necessary for a better understanding of the mechanisms of hearing loss and vestibular dysfunction caused by GRXCR1 mutations.

scholarly journals USH2 Caused by GPR98 Mutation Diagnosed by Massively Parallel Sequencing in Advance of the Occurrence of Visual Symptoms

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 123S-128S ◽  
Author(s):  
Hideaki Moteki ◽  
Hidekane Yoshimura ◽  
Hela Azaiez ◽  
Kevin T. Booth ◽  
A. Eliot Shearer ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Massively Parallel Sequencing ◽  
Usher Syndrome ◽  
Genetic Diagnosis ◽  
Massively Parallel ◽  
Parallel Sequencing ◽  
Visual Symptoms ◽  
Targeted Genomic Enrichment ◽  
Usher Syndrome Type

Objective: We present 2 patients who were identified with mutations in the GPR98 gene that causes Usher syndrome type 2 (USH2). Methods: One hundred ninety-four (194) Japanese subjects from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were used to identify the genetic causes of hearing loss. Results: We identified causative mutations in the GPR98 gene in 1 family (2 siblings). The patients had moderate sloping hearing loss, and no progression was observed over a period of 10 years. Fundus examinations were normal. However, electroretinograms revealed impaired responses in both patients. Conclusion: Early diagnosis of Usher syndrome has many advantages for patients and their families. This study supports the use of comprehensive genetic diagnosis for Usher syndrome, especially prior to the onset of visual symptoms, to provide the highest chance of diagnostic success in early life stages.

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