scholarly journals 5′ UTR CGG repeat expansion in GIPC1 is associated with oculopharyngodistal myopathy

Brain ◽  
2020 ◽  
Author(s):  
Jianying Xi ◽  
Xilu Wang ◽  
Dongyue Yue ◽  
Tonghai Dou ◽  
Qunfeng Wu ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Trinucleotide Repeat ◽  
Late Onset ◽  
Age At Onset ◽  
Large Family ◽  
Repeat Expansion ◽  
Chain Reaction ◽  
Cgg Repeat ◽  
Sporadic Cases ◽  
Polymerase Chain

Abstract Oculopharyngodistal myopathy is a late-onset degenerative muscle disorder characterized by ptosis and weakness of the facial, pharyngeal, and distal limb muscles. A recent report suggested a non-coding trinucleotide repeat expansion in LRP12 to be associated with the disease. Here we report a genetic study in a Chinese cohort of 41 patients with the clinical diagnosis of oculopharyngodistal myopathy (21 cases from seven families and 20 sporadic cases). In a large family with 12 affected individuals, combined haplotype and linkage analysis revealed a maximum two-point logarithm of the odds (LOD) score of 3.3 in chromosomal region chr19p13.11-p13.2 and narrowed the candidate region to an interval of 4.5 Mb. Using a comprehensive strategy combining whole-exome sequencing, long-read sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal CGG repeat expansion in the 5′ UTR of the GIPC1 gene that co-segregated with disease. Overall, the repeat expansion in GIPC1 was identified in 51.9% independent pedigrees (4/7 families and 10/20 sporadic cases), while the repeat expansion in LRP12 was only identified in one sporadic case (3.7%) in our cohort. The number of CGG repeats was <30 in controls but >60 in affected individuals. There was a slight correlation between repeat size and the age at onset. Both repeat expansion and retraction were observed during transmission but somatic instability was not evident. These results further support that non-coding CGG repeat expansion plays an essential role in the pathogenesis of oculopharyngodistal myopathy.

A Novel Polymorphism in the FMR1 Gene: Implications for Clinical Testing of Fragile X Syndrome

2008 ◽  
Vol 132 (1) ◽  
pp. 95-98
Author(s):  
Bharat Thyagarajan ◽  
Matthew Bower ◽  
Michael Berger ◽  
Sidney Jones ◽  
Michelle Dolan ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Southern Blot ◽  
Trinucleotide Repeat ◽  
Fragile X ◽  
Fmr1 Gene ◽  
Chain Reaction ◽  
Cgg Repeat ◽  
Polymerase Chain

Abstract Fragile X syndrome is the most common cause of inherited mental retardation among males. In most cases, the molecular basis of fragile X syndrome is the expansion and subsequent methylation of a CGG trinucleotide repeat in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene. Laboratory diagnosis usually relies on a combination of Southern blot and polymerase chain reaction analyses. In this case report we describe an unusual Southern blot result in a patient who presented with developmental delay and had a normal CGG repeat number by polymerase chain reaction analysis. Further investigation revealed a novel G3310C transversion in the FMR1 gene resulting in a new recognition site for the BssHII restriction enzyme. This novel restriction site could potentially mimic a partial deletion of the FMR1 gene on Southern blot analysis and thus represents a possible pitfall in the diagnosis of fragile X syndrome.

scholarly journals Screening A Trinucleotide Repeat Expansion: How precise PCR can be?

2019 ◽  
Vol 3 (3) ◽  
pp. 34-40
Author(s):  
Ziske Maritska ◽  
Baharudin Baharudin ◽  
Ardy Santosa ◽  
Ching Leng Kee ◽  
Tan Yue Ming ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Trinucleotide Repeat ◽  
Repeat Expansion ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Chain Reaction ◽  
Trinucleotide Repeat Expansion ◽  
Pcr Method ◽  
The Mean ◽  
Polymerase Chain

ABSTRACT Background. Trinucleotide Repeat Expansion (TRE) in human DNA could lead to various diseases. An expanded CAG repeat (>31 or 37 repeats, depends on the ethnicity) in Androgen Receptor gene is suggested to be associated with the occurrence of isolated hypospadias. In an effort to identify the exact numbers of repeats, sequencing has been the most favored method to be conducted despite its cost. Objective. This study wished to investigate the possibilities of using Polymerase Chain Reaction (PCR) method to screen expanded repeats in isolated hypospadias, as one of the TRE diseases. Materials and Methods. Numbers of CAG repeat in twelve hypospadias patients and one normal male was first predicted from the visualization of PCR products in 3% agarose gel electrophoreses with 20 bp ladder marker before it was finally sequenced. Results. Two samples gave the same exact result, while the rest showed a range of 1-11 bp differences. Statistically, there was a significant difference between the mean of CAG repeats from PCR method (M=26.1667, SD=6.71272) and the mean of CAG repeats from sequencing (M=23.75, SD=5.70685); t(11)= 4.570, p=0.001. Furthermore, the sensitivity of PCR was 100% and the specificity was 83.33%. Conclusion. It can be concluded that PCR method could be used as a screening method in identifying TRE with large numbers of repeats. However, PCR in TRE disease with small numbers of expanded repeats needs to be followed by sequencing in order to obtain the exact numbers of repeats.   Keywords: Trinucleotide Repeat Expansion, Polymerase Chain Reaction, Sequencing, Isolated Hypospadias

Molecular typing of Lactobacillus brevis isolates from Korean food using repetitive element-polymerase chain reaction

2018 ◽  
Vol 24 (4) ◽  
pp. 341-350 ◽  
Author(s):  
Jasmine Kaur ◽  
Anshul Sharma ◽  
Sulhee Lee ◽  
Young-Seo Park
Keyword(s):  
Polymerase Chain Reaction ◽  
Repetitive Element ◽  
Bacterial Species ◽  
Large Family ◽  
Lactobacillus Brevis ◽  
Polymerase Chain Reaction Method ◽  
Fermented Foods ◽  
Chain Reaction ◽  
Easy Method ◽  
Polymerase Chain

Lactobacillus brevis is a part of a large family of lactic acid bacteria that are present in cheese, sauerkraut, sourdough, silage, cow manure, feces, and the intestinal tract of humans and rats. It finds its use in food fermentation, and so is considered a “generally regarded as safe” organism. L. brevis strains are extensively used as probiotics and hence, there is a need for identifying and characterizing these strains. For identification and discrimination of the bacterial species at the subspecific level, repetitive element-polymerase chain reaction method is a reliable genomic fingerprinting tool. The objective of the present study was to characterize 13 strains of L. brevis isolated from various fermented foods using repetitive element-polymerase chain reaction. Repetitive element-polymerase chain reaction was performed using three primer sets, REP, Enterobacterial Repetitive Intergenic Consensus (ERIC), and (GTG)5, which produced different fingerprinting patterns that enable us to distinguish between the closely related strains. Fingerprinting patterns generated band range in between 150 and 5000 bp with REP, 200–7500 bp with ERIC, and 250–2000 bp with (GTG)5 primers, respectively. The Jaccard’s dissimilarity matrices were used to obtain dendrograms by the unweighted neighbor-joining method using genetic dissimilarities based on repetitive element-polymerase chain reaction fingerprinting data. Repetitive element-polymerase chain reaction proved to be a rapid and easy method that can produce reliable results in L. brevis species.

scholarly journals Dynamic mutations pose unique challenges for the molecular diagnostics laboratory

1996 ◽  
Vol 42 (10) ◽  
pp. 1582-1588 ◽  
Author(s):  
R C McGlennen
Keyword(s):  
Polymerase Chain Reaction ◽  
Molecular Diagnostics ◽  
Diagnostic Tests ◽  
Trinucleotide Repeat ◽  
Molecular Testing ◽  
Ethical Challenges ◽  
Clinical Context ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Dynamic Mutations

Abstract Routine clinical molecular testing of diseases associated with unstable or dynamic trinucleotide repeat syndromes poses unique technical, medical, and ethical challenges to the laboratory. Although the pathophysiology of these disorders is to date still largely undefined, the uniformity of their genetics has led to the development of highly informative diagnostic tests. In general, amplification techniques, such as the polymerase chain reaction (PCR), are used to determine the size of alleles within the genes linked to these disorders. Technically, these assays require empirical optimization so that the PCR reactions are both robust and reproducible, and occasionally other methods must be used to confirm diagnoses. Beyond execution of the test, however, the molecular diagnostics laboratory needs also to be fundamentally involved in the process of interpreting these tests in the correct clinical context and in setting policy as to how these data are presented to patients.

scholarly journals Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor

Brain ◽  
2019 ◽  
Vol 143 (1) ◽  
pp. 222-233 ◽  
Author(s):  
Qi-Ying Sun ◽  
Qian Xu ◽  
Yun Tian ◽  
Zheng-Mao Hu ◽  
Li-Xia Qin ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Essential Tremor ◽  
Repeat Expansion ◽  
Chain Reaction ◽  
Comprehensive Strategy ◽  
Whole Exome ◽  
High Prevalence ◽  
Long Read ◽  
Polymerase Chain ◽  
Human Specific

Abstract Essential tremor is one of the most common movement disorders. Despite its high prevalence and heritability, the genetic aetiology of essential tremor remains elusive. Up to now, only a few genes/loci have been identified, but these genes have not been replicated in other essential tremor families or cohorts. Here we report a genetic study in a cohort of 197 Chinese pedigrees clinically diagnosed with essential tremor. Using a comprehensive strategy combining linkage analysis, whole-exome sequencing, long-read whole-genome sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal GGC repeat expansion in the 5′ region of the NOTCH2NLC gene that co-segregated with disease in 11 essential tremor families (5.58%) from our cohort. Clinically, probands that had an abnormal GGC repeat expansion were found to have more severe tremor phenotypes, lower activities of daily living ability. Obvious genetic anticipation was also detected in these 11 essential tremor-positive families. These results indicate that abnormal GGC repeat expansion in the 5′ region of NOTCH2NLC gene is associated with essential tremor, and provide strong evidence that essential tremor is a family of diseases with high clinical and genetic heterogeneities.

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