Deletional mutations of dystrophin gene and carrier detection in eastern India

Basak, Jayasri; Dasgupta, Uma B.; Mukherjee, Susmita; Das, Shyamal Kumar; Senapati, Asit Kumar; Banerjee, Tapas Kumar

doi:10.1007/s12098-009-0214-y

Cited by 11 publications

(4 citation statements)

References 22 publications

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“…In relation to the PCR method, the MLPA method revealed 3 larger deletions, 4 deletions outside of the "hot spots" in the gene and 4 duplications in the probands, which confirms the effectiveness of the MLPA method in the detection of deletions/duplications in the dystrophin gene [11,[20][21][22]. The largest number of mutations was localized in the distal part of the gene (exons 45-55) in 61.3% (19/31) of cases, which is the most common localisation of deletions/duplications in sporadic DMD/BMD cases [23].…”

Section: Discussionsupporting

confidence: 63%

The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies

et al. 2023

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Background/Aim. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. They are X-linked recessive diseases, where males are affected and females are mostly healthy carriers of the mutation. It is estimated that 2/3 mothers of DMD probands are carriers, while 1/3 of patients have de novo mutations. The aim was to confirm the carrier status of females in the families of DMD/BMD probands, using direct genetic methods. Methods. We tested 38 females from 31 families of DMD/BMD probands with deletion/duplication in the dystrophin gene. Also, 4 cases of prenatal diagnosis of DMD/BMD were included. We preformed the polymerase chain reaction (PCR) and the multiplex ligation-dependent method (MLPA) for deletion detection, i.e. deletion/duplication in the dystrophin gene. Results. In 31 DMD/BMD probands, we identified 87.1% deletions and 12.9% duplications of one or more exons. Of the 29 tested mothers, mutations were found in 17 (14 deletions and 3 duplications). Mutations were found in 57.9% (11/19) mothers of DMD and in 60% (6/10) mothers of BMD, respectively. Also, in probands with deletions 56% (14/25) of mothers were carries and in probands with duplications 3 mothers of 4 (75%). Of the 9 other female relatives, mutations were found in 4. In prenatal diagnosis, we identified deletion in one male and one female foetus of one mother. Conclusion. The study showed that mothers were carriers in almost 60% of sporadic cases of DMD/BMD with deletions and duplication. Also, the carrier frequency tended to be higher in mothers of the probands with duplication (75%) then in probands with deletions (56%). In the case of a mother who was confirmed as a carrier, deletion was detected in 2 of 3 foetuses.

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Section: Discussionsupporting

confidence: 63%

The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies

et al. 2023

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“…However, we could not validate the SEdel/dup by sequencing which may have revealed potential polymorphism or point mutation in the probe binding site. In a study conducted in the East Indian region, although the deletion rate of 65.7% was reported, deletion in the distal hot spot exonic region was noted in 82.61% of cases and that in the proximal hotspot, region was 10.87% [29]. In a South Indian MLPA based study, Vengalil et al reported deletions and duplications in 91% and 9% cases, respectively from a cohort of 279 DMD subjects [30] and reported exon 50 deletion to be the most common mutation.…”

Section: Discussionmentioning

confidence: 90%

Repurposing Pathogenic Variants of DMD Gene and its Isoforms for DMD Exon Skipping Intervention

Tyagi

Kumar

Dalal

et al. 2020

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Background: Duchenne Muscular Dystrophy (DMD) is a progressive, fatal neuromuscular disorder caused by mutations in the DMD gene. Emerging antisense oligomer based exon skipping therapy provides hope for the restoration of the reading frame. Objectives: Population-based DMD mutation database may enable exon skipping to be used for the benefit of patients. Hence, we planned this study to identify DMD gene variants in North Indian DMD cases. Methods: A total of 100 DMD cases were recruited and Multiplex ligation-dependent probe amplification (MLPA) analysis was performed to obtain the deletion and duplication profile. Results: Copy number variations (deletion/duplication) were found in 80.85% of unrelated DMD cases. Sixty-eight percent of cases were found to have variations in the distal hotspot region (Exon 45- 55) of the DMD gene. Exon 44/45 variations were found to be the most prominent among single exon variations, whereas exon 49/50 was found to be the most frequently mutated locations in single/ multiple exon variations. As per Leiden databases, 86.84% cases harboured out-of-frame mutations. Domain wise investigation revealed that 68% of mutations were localized in the region of spectrin repeats. Dp140 isoform was predicted to be absent in 62/76 (81.57%) cases. A total of 45/80 (56.25 %) and 23/80 (28.70%) DMD subjects were predicted to be amenable to exon 51 and exon 45 skipping trials, respectively. Conclusion: A major proportion of DMD subjects (80%) could be diagnosed by the MLPA technique. The data generated from our study may be beneficial for strengthening of mutation database in the North Indian population.

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“…Reported deletion detection rates vary widely, ranging between 31% and 73.86%. 11 – 24 These differences may be caused by many factors such as race, sample size and inclusion criteria. It has been suggested that the relatively low deletion detection rate in some studies is caused by the inclusion of other similar muscle diseases, because diagnosis was based mainly on clinical symptoms and did not require muscle biopsy.…”

Section: Discussionmentioning

confidence: 99%

Distribution of dystrophin gene deletions in a Chinese population

Liu

Ouyang

et al. 2016

J Int Med Res

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ObjectiveTo describe the deletion patterns and distribution characteristics of the dystrophin gene in a Chinese population of patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD).MethodsPatients with DMD/BMD were recruited. Deletions in 19 exons of the dystrophin gene were evaluated using accurate multiplex polymerase chain reaction (PCR).ResultMultiplex PCR identified deletions in 238/401 (59.4%) patients with DMD/BMD. Of these, 196 (82.4%) were in the distal hotspot, 32 (13.4%) were in the proximal hotspot, five (2.1%) were in both regions and five (2.1%) were in neither hotspot. Deletions were classified into 54 patterns. Exon 49 was the most frequently deleted. The reading frame rule was upheld for 91.9% of cases.ConclusionAccurate multiplex PCR for 19 exons is an effective diagnostic tool.

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Deletional mutations of dystrophin gene and carrier detection in eastern India

Abstract: About half the mothers of affected probands were not carriers of the deletion, underscoring the need to use real time techniques for carrier detection.

Cited by 11 publications

References 22 publications

The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies

The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies

Repurposing Pathogenic Variants of DMD Gene and its Isoforms for DMD Exon Skipping Intervention

Distribution of dystrophin gene deletions in a Chinese population

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