Single amino acid loss in the dystrophin protein associated with a mild clinical phenotype

Pons, Roser; Kekou, Kyriaki; Gkika, Artemis; Papadimas, George K.; Vogiatzakis, N.; Svingou, Maria; Papadopooulos, Constantinos; Nikas, Ioanis; Dinopoulos, Argirios; Youroukos, Sotiris; Kanavakis, Emmanouel

doi:10.1002/mus.25190

Cited by 5 publications

(3 citation statements)

References 11 publications

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“…The haplotype study in our series revealed that all index case groups harboring the same BP originated from distinct founder mutations, except for the D1 group, which turned out to be the result of 2 independent founder mutation events. The high rate of founder effects observed in our series contrasts with their rare occurrence in the BMD disease population, as only 2 similar founder effects occur have been reported 43,44 . In any case, this phenomenon is indicative of the preservation of fertility.…”

Section: Discussioncontrasting

confidence: 65%

“…The high rate of founder effects observed in our series contrasts with their rare occurrence in the BMD disease population, as only 2 similar founder effects occur have been reported. 43,44 In any case, this phenomenon is indicative of the preservation of fertility. On the other hand, this observation provided us with the chance to dispose of groups with sufficient size to enable the comparison of the effect of BP locations on the outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45–55 Deletion

Poyatos-García

Martí

Liquori

et al. 2022

Annals of Neurology

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Duchenne muscular dystrophy (DMD) exon 45-55 deletion (del45-55) has been postulated as a model that could treat up to 60% of DMD patients, but the associated clinical variability and complications require clarification. We aimed to understand the phenotypes and potential modifying factors of this dystrophinopathy subset. Methods: This cross-sectional, multicenter cohort study applied clinical and functional evaluation. Next generation sequencing was employed to identify intronic breakpoints and their impact on the Dp140 promotor, intronic long noncoding RNA, and regulatory splicing sequences. DMD modifiers (SPP1, LTBP4, ACTN3) and concomitant mutations were also assessed. Haplotypes were built using DMD single nucleotide polymorphisms. Dystrophin expression was

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Section: Discussioncontrasting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45–55 Deletion

Poyatos-García

Martí

Liquori

et al. 2022

Annals of Neurology

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“…Interestingly, in the frequently reported cases, the simple insertion or substitution mutations are more likely to resided in different Spectrins repeats within the Central Rod domain (Fig. 5c) [40][41][42], indicating that the possible significant anchoring or binding functions are important for maintaining the abundance and activity of dystrophy. Indeed, Multiple-polymorphic sites were found within the coding region of DMD and the reduced expression level of dystrophin is associated with the incidence of DMD [43].…”

Section: Discussionmentioning

confidence: 98%

Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report

et al. 2020

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Abstracts Background Duchenne muscular dystrophies (DMDs) are X-linked recessive neuromuscular disorders with malfunction or absence of the Dystrophin protein. Precise genetic diagnosis is critical for proper planning of patient care and treatment. In this study, we described a Chinese family with mosaic DMD mutations and discussed the best method for prenatal diagnosis and genetic counseling of X-linked familial disorders. Methods We investigated all variants of the whole dystrophin gene using multiple DNA samples isolated from the affected family and identified two variants of the DMD gene in a sick boy and two female carriers by targeted next generation sequencing (TNGS), Sanger sequencing, and haplotype analysis. Results We identified the hemizygous mutation c.6794delG (p.G2265Efs*6) of DMD in the sick boy, which was inherited from his mother. Unexpectedly, a novel heterozygous mutation c.6796delA (p.I2266Ffs*5) of the same gene, which was considered to be a de novo variant, was detected from his younger sister instead of his mother by Sanger sequencing. However, further NGS analysis of the mother and her amniotic fluid samples revealed that the mother carried a low-level mosaic c.6796delA mutation. Conclusions We reported two different mutations of the DMD gene in two siblings, including the novel mutation c.6796delA (p.I2266Ffs*5) inherited from the asymptomatic mosaic-carrier mother. This finding has enriched the knowledge of the pathogenesis of DMD. If no mutation is detected in obligate carriers, the administration of intricate STR/NGS/Sanger analysis will provide new ideas on the prenatal diagnosis of DMD.

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Evidence-Based Consensus and Systematic Review on Reducing the Time to Diagnosis of Duchenne Muscular Dystrophy

Aartsma‐Rus

Hegde

Ben‐Omran

et al. 2019

The Journal of Pediatrics

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Section 1: Reducing the time to diagnosis of DMD Statement 1: The following signs, symptoms, and characteristics should be considered typical indicators of DMD: calf hypertrophy (pseudohypertrophy); delayed walking; difficulty climbing/descending stairs; difficulty rising from the floor; difficulty running/walking; elevated serum CK levels (including elevated ALT and AST); a family history of DMD; frequent falls; Gowers' sign; male sex; and muscle weakness. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CGH, comparative genome hybridization; CK, creatine kinase; DMD, Duchenne muscular dystrophy; GRADE, Grading of Recommendations Assessment, Development, and Evaluation. *The level of evidence for most of the statements was graded as either low or moderate, owing to the fact that most of the studies included here are observational in nature rather than randomized controlled trials (due to the nature of this initiative). When there were multiple corroborative supporting observational studies, we have selected "moderate" for quality of evidence. †Consensus: A + = strongly agree; A = agree; N = neither agree nor disagree; D = disagree; D + = strongly disagree. Grade of recommendation: 1A = strong recommendation, high-quality evidence; 1B = strong recommendation, moderate-quality evidence; 1C = strong recommendation, low-quality or very low-quality evidence; 2A = weak recommendation, high-quality evidence; 2B = weak recommendation, moderate-quality evidence; 2C = weak recommendation, low-quality or very low-quality evidence. ‡Where applicable depending on country-specific legislation on presymptomatic testing of patients aged ≤18 years.

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Single amino acid loss in the dystrophin protein associated with a mild clinical phenotype

Abstract: The c.5068_5070delCAC locus in the DMD gene is associated with a very mild phenotype. Further study is needed to evaluate disease progression in these patients. Muscle Nerve 55: 46-50, 2017.

Cited by 5 publications

References 11 publications

Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45–55 Deletion

Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45–55 Deletion

Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report

Evidence-Based Consensus and Systematic Review on Reducing the Time to Diagnosis of Duchenne Muscular Dystrophy

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