scholarly journals Retinoblastoma genetics screening and clinical management

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Himika Gupta ◽  
Sivasankar Malaichamy ◽  
Ashwin Mallipatna ◽  
Sakthivel Murugan ◽  
Nallathambi Jeyabalan ◽  
...  
Keyword(s):  
Clinical Management ◽  
Detection Rate ◽  
Mutation Detection ◽  
Gene Mutations ◽  
Disease Recurrence ◽  
Germline Mutations ◽  
Global Studies ◽  
Mutation Detection Rate ◽  
Gene Deletions

Abstract Background India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored. Methods Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence. Results Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy. Conclusions We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.

scholarly journals Retinoblastoma Mutational Screening in India: Opportunities and Challenges in Clinical Decisions and Genetic Counselling

2021 ◽  
Author(s):  
Himika Gupta ◽  
Sivasankar Malaichamy ◽  
Ashwin Mallipatna ◽  
Sakthivel Murugan ◽  
Nallathambi Jeyabalan ◽  
...  
Keyword(s):  
Clinical Management ◽  
Detection Rate ◽  
Mutation Detection ◽  
Gene Mutations ◽  
Disease Recurrence ◽  
Germline Mutations ◽  
Clinical Decisions ◽  
Mutation Detection Rate ◽  
Gene Deletions ◽  
Mutational Screening

Abstract Background: India accounts for 20% of the global retinoblastoma (RB) burden. Existing data is sparse on RB1 gene germline mutations and its influence on clinical decisions is minimally explored. Methods: Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity and recurrence. Results: Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands (79%), inclusive of 3 novel mutations, previously reported 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p=0.021), progression (p=0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy. Conclusions: We identified novel RB1 mutations and our mutation detection rate was at par with previous robust global studies. Genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India.

scholarly journals Diverse Genetic Landscape of Suspected Retinitis Pigmentosa in a Large Korean Cohort

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 675
Author(s):  
Yoon-Jeon Kim ◽  
You-Na Kim ◽  
Young-Hee Yoon ◽  
Eul-Ju Seo ◽  
Go-Hun Seo ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Detection Rate ◽  
Mutation Detection ◽  
Retinal Disease ◽  
Mutation Detection Rate ◽  
Targeted Next Generation Sequencing ◽  
Initial Symptoms ◽  
Genetic Landscape ◽  
History Of ◽  
Genetic Profiles

We conducted targeted next-generation sequencing (TGS) and/or whole exome sequencing (WES) to assess the genetic profiles of clinically suspected retinitis pigmentosa (RP) in the Korean population. A cohort of 279 unrelated Korean patients with clinically diagnosed RP and available family members underwent molecular analyses using TGS consisting of 88 RP-causing genes and/or WES with clinical variant interpretation. The combined genetic tests (TGS and/or WES) found a mutation in the 44 RP-causing genes and seven inherited retinal disease (IRD)-causing genes, and the total mutation detection rate was 57%. The mutation detection rate was higher in patients who experienced visual deterioration at a younger age (75.4%, age of symptom onset under 10 years) and who had a family history of RP (70.7%). The most common causative genes were EYS (8.2%), USH2A (6.8%), and PDE6B (4.7%), but mutations were dispersed among the 51 RP/IRD genes generally. Meanwhile, the PDE6B mutation was the most common in patients experiencing initial symptoms in their first decade, EYS in their second to third decades, and USH2A in their fifth decades and older. Of note, WES revealed some unexpected genotypes: ABCC6, CHM, CYP4V2, RS1, TGFBI, VPS13B, and WDR19, which were verified by ophthalmological re-phenotyping.

Independent mutational events are rare in the ATM gene: Haplotype prescreening enhances mutation detection rate

2003 ◽  
Vol 22 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Midori Mitui ◽  
Catarina Campbell ◽  
Gabriela Coutinho ◽  
Xia Sun ◽  
Chih-Hung Lai ◽  
...  
Keyword(s):  
Detection Rate ◽  
Mutation Detection ◽  
Mutation Detection Rate ◽  
Atm Gene ◽  
Gene Haplotype

Spectrum of molecular defects and mutation detection rate in patients with severe hemophilia A

2005 ◽  
Vol 26 (3) ◽  
pp. 249-254 ◽  
Author(s):  
Nadja Bogdanova ◽  
Arseni Markoff ◽  
Hartmut Pollmann ◽  
Ulrike Nowak-Göttl ◽  
Roswith Eisert ◽  
...  
Keyword(s):  
Detection Rate ◽  
Mutation Detection ◽  
Hemophilia A ◽  
Severe Hemophilia ◽  
Mutation Detection Rate ◽  
Molecular Defects

An investigation of PIK3CA mutations in isolated macrodactyly

2018 ◽  
Vol 43 (7) ◽  
pp. 756-760 ◽  
Author(s):  
Jingheng Wu ◽  
Wei Tian ◽  
Guanglei Tian ◽  
Kelli Sumner ◽  
Douglas T. Hutchinson ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Molecular Mechanism ◽  
Mutation Analysis ◽  
Detection Rate ◽  
Mutation Detection ◽  
Pik3ca Mutation ◽  
Mutation Detection Rate ◽  
Pik3ca Mutations ◽  
Diagnosis And Classification ◽  
Set Up

Somatic PIK3CA mutations may relate to pathogenesis of isolated macrodactyly. We set up to test the association between PIK3CA mutations with isolated macrodactyly in order to establish a more accurate and molecular mechanism-based diagnosis and classification. DNA extracted from affected tissues in 12 individuals with isolated macrodactyly was tested for PIK3CA mutation using targeted Sanger DNA sequencing. Ten patients had macrodactyly in the foot and two in the hand. Nine of the 12 patients were found to carry a low-level, mosaic PIK3CA mutation. The mutations identified, p.His1047Arg, p.His1047Leu, p.Glu545Lys, and p.Glu542Lys, are codons frequently mutated in cancers. Among all tissues tested, adipose had the highest mutation detection rate, followed by nerve and skin. Our results indicate that a high proportion of isolated macrodactyly patients carry a pathogenic PIK3CA mutation. Affected adipose, nerve and skin tissues are ideal for PIK3CA mutation analysis.

Detection of BRAF mutations in melanoma: Rate of mutation detection at codon 600 using Sanger sequencing as compared to the cobas 4800 method.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8596-8596
Author(s):  
Kevin Z. Qu ◽  
Qiulu Pan ◽  
Xi Zhang ◽  
Luis Rodriguez ◽  
Jennifer Uyeji ◽  
...  
Keyword(s):  
Molecular Diagnostics ◽  
Sanger Sequencing ◽  
Detection Rate ◽  
Mutation Detection ◽  
Mutation Detection Rate ◽  
Braf Mutations ◽  
Roche Molecular Diagnostics ◽  
Ffpe Tissues ◽  
Sanger Method ◽  
Braf V600 Mutation

8596 Background: Detection of BRAF V600 mutations is currently a prerequisite for approved use of vemurafenib in patients with metastatic melanoma. The cobas 4800 BRAF V600 Mutation Test (Roche Molecular Diagnostics), a PCR-based assay approved to aid in selecting patients for vemurafenib therapy, primarily detects V600E. It is also reported to detect V600K, which has been associated with vemurafenib response as well. We compared the mutation detection rate of the cobas assay with that of Sanger sequencing. Methods: 125 de-identified FFPE tissues submitted for BRAF mutation analysis that all showed histologically-confirmed melanoma were tested. BRAF mutations were detected using both the cobas kit and bidirectional Sanger sequencing using BigDye kits (Applied Biosystems). DNA was extracted from 5-um sections without macrodissection using the cobas DNA extraction kit (for the cobas test) or from 5-10-um sections using Agencourt extraction kits (Beckman Coulter) following macrodissection. Results: The two methods showed agreement in 104/125 (83.2%) of cases (Table). Sanger sequencing detected V600 dinucleotide mutations in 9 samples that were negative by the cobas assay. Sanger sequencing produced no results in 10 cases owing to suboptimal PCR, including 2 that were positive by the cobas assay. The cobas assay produced 2 invalid results, including 1 that was positive for V600E by Sanger.The cobas assay detected 7/11 V600K mutations. Conclusions: Overall agreement between cobas and Sanger sequencing was 83.2%. The Sanger method had higher analytic sensitivity, resulting in nine additional V600 mutations not called by cobas compared to the two seen by cobas but not Sanger sequencing. Thus, 16% (9/57) more patients would be identified as candidates for vemurafenib therapy using the Sanger method. [Table: see text]

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