scholarly journals Gestational Outcomes of Pregnant Women Who Have Had Invasive Prenatal Testing for the Prenatal Diagnosis of Duchenne Muscular Dystrophy

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Mehmet Sinan Beksac ◽  
Atakan Tanacan ◽  
Duygu Aydin Hakli ◽  
Gokcen Orgul ◽  
Burcu Soyak ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Chorionic Villus ◽  
Gene Mutations ◽  
Diagnostic Methods ◽  
Obstetric Outcomes ◽  
Chorionic Villus Sampling ◽  
Significant Difference ◽  
Dmd Gene

Aim. To show the importance of prenatal diagnosis of Duchenne Muscular Dystrophy (DMD) and to demonstrate the effect of DMD gene mutations on gestational outcomes. Materials and Methods. We retrospectively evaluated 89 pregnancies in 81 individuals who were referred to Hacettepe University for prenatal diagnosis of DMD between January 2000 and December 2015. Prenatal diagnostic methods (chorionic villus sampling (CVS): 66, amniocentesis (AC): 23) were compared for test results, demographic features, and obstetric outcomes of pregnancies. The female fetuses were divided into two groups according to the DMD status (healthy or carrier) to understand the effect of DMD gene mutations on obstetric outcomes. Results. Eight prenatally diagnosed disease-positive fetuses were terminated. There was no statistically significant difference between the CVS and AC groups in terms of study variables. There were 46 male fetuses (51.6%) and 43 female fetuses (48.4%). Fifteen of the female fetuses were carriers (34.8%). Median birthweight values were statistically insignificantly lower in the carrier group. Conclusion. Pregnancies at risk for DMD should be prenatally tested to prevent the effect of disease on families and DMD carrier fetuses had obstetric outcomes similar to DMD negative female fetuses.

scholarly journals Noninvasive Prenatal Diagnosis for Duchenne Muscular Dystrophy Based on the Direct Haplotype Phasing

2019 ◽  
Author(s):  
Min Chen ◽  
Chao Chen ◽  
Xiaoyan Huang ◽  
Jun Sun ◽  
Lu Jiang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Chorionic Villus ◽  
Chorionic Villus Sampling ◽  
Singleton Pregnancy ◽  
High Molecular Weight Dna ◽  
Haplotype Phasing ◽  
Noninvasive Prenatal Diagnosis ◽  
Mutational Status

AbstractObjectiveWe aimed to investigate the validity of noninvasive prenatal diagnosis (NIPD) based on direct haplotype phasing without the proband and its feasibility for clinical application in the case of Duchenne Muscular Dystrophy (DMD).MethodsThirteen singleton-pregnancy families affected by DMD were recruited. Firstly, we resolved maternal haplotypes for each family by performing targeted linked-read sequencing of their high molecular weight DNA, respectively. Then, we identified SNPs of the DMD gene in all carrier mothers and inferred the DMD gene mutation status of all fetuses. Finally, the fetal genotypes were further validated by using chorionic villus sampling.ResultsThe method of directly resolving maternal haplotype through targeted linked-read sequencing was smoothly performed in all participated families. The predicted mutational status of 13 fetuses was correct, which had been confirmed by invasive prenatal diagnosis.ConclusionDirect haplotyping of NIPD based on linked-read sequencing for DMD is accurate.

scholarly journals Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China

2021 ◽  
Vol 12 ◽  
Author(s):  
Lingrong Kong ◽  
Shaojun Li ◽  
Zhenhua Zhao ◽  
Jun Feng ◽  
Guangquan Chen ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Family Members ◽  
Chorionic Villus ◽  
Genetic Diagnosis ◽  
Blood Collection ◽  
Chorionic Villus Sampling ◽  
Clinical Environment ◽  
Noninvasive Prenatal Diagnosis

Noninvasive prenatal diagnosis (NIPD) of single-gene disorders has recently become the focus of clinical laboratories. However, reports on the clinical application of NIPD of Duchenne muscular dystrophy (DMD) are limited. This study aimed to evaluate the detection performance of haplotype-based NIPD of DMD in a real clinical environment. Twenty-one DMD families at 7–12 weeks of gestation were prospectively recruited. DNA libraries of cell-free DNA from the pregnant and genomic DNA from family members were captured using a custom assay for the enrichment of DMD gene exons and spanning single-nucleotide polymorphisms, followed by next-generation sequencing. Parental haplotype phasing was based on family linkage analysis, and fetal genotyping was inferred using the Bayes factor through target maternal plasma sequencing. Finally, the entire experimental process was promoted in the local clinical laboratory. We recruited 13 complete families, 6 families without paternal samples, and 2 families without probands in which daughter samples were collected. Two different maternal haplotypes were constructed based on family members in all 21 pedigrees at as early as 7 gestational weeks. Among the included families, the fetal genotypes of 20 families were identified at the first blood collection, and a second blood collection was performed for another family due to low fetal concentration. The NIPD result of each family was reported within 1 week. The fetal fraction in maternal cfDNA ranged from 1.87 to 11.68%. In addition, recombination events were assessed in two fetuses. All NIPD results were concordant with the findings of invasive prenatal diagnosis (chorionic villus sampling or amniocentesis). Exon capture and haplotype-based NIPD of DMD are regularly used for DMD genetic diagnosis, carrier screening, and noninvasive prenatal diagnosis in the clinic. Our method, haplotype-based early screening for DMD fetal genotyping via cfDNA sequencing, has high feasibility and accuracy, a short turnaround time, and is inexpensive in a real clinical environment.

scholarly journals Detection of Duchenne muscular dystrophy gene products in amniotic fluid and chorionic villus sampling cells

FEBS Letters ◽  
1993 ◽  
Vol 335 (2) ◽  
pp. 223-230 ◽  
Author(s):  
Hagit Prigojin ◽  
Marina Brusel ◽  
Ora Fuchs ◽  
Ruth Shomrat ◽  
Cyril Legum ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Amniotic Fluid ◽  
Chorionic Villus ◽  
Chorionic Villus Sampling ◽  
Gene Products ◽  
Duchenne Muscular Dystrophy Gene

scholarly journals Comparison of Long-term Ambulatory Function in Patients with Duchenne Muscular Dystrophy Treated with Eteplirsen and Matched Natural History Controls

2021 ◽  
pp. 1-11
Author(s):  
Jerry R. Mendell ◽  
Navid Khan ◽  
Nanshi Sha ◽  
Helen Eliopoulos ◽  
Craig M. McDonald ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gene Mutations ◽  
Exon Skipping ◽  
Term Treatment ◽  
Long Term Treatment ◽  
The Difference ◽  
Dmd Gene ◽  
6 Minute Walk Test

Background: Duchenne muscular dystrophy (DMD) is a rare, X-linked, fatal, degenerative neuromuscular disease caused by DMD gene mutations. A relationship between exon skipping and dystrophin production in exon 51-amenable patients treated with eteplirsen (EXONDYS 51 ®) is established. Once-weekly eteplirsen significantly increased dystrophin, with slower decline in ambulatory function compared to baseline. Long-term treatment with eteplirsen leads to accumulation of dystrophin over time and observed functional benefits in patients with DMD. Objective: Compare long-term ambulatory function in eteplirsen-treated patients versus controls. Methods: Study 201/202 included 12 eteplirsen-treated patients assessed twice/year for ambulatory function over 4 years. Ambulatory evaluations (6-minute walk test [6MWT], loss of ambulation, and North Star Ambulatory Assessment [NSAA]) were compared with matched controls from Italian Telethon and Leuven registries. Results: At Years 3 and 4, eteplirsen-treated patients demonstrated markedly greater mean 6MWT than controls (difference in change from baseline of 132 m [95%CI (29, 235), p = 0.015] at Year 3 and 159 m [95%CI (66, 253), p = 0.002] at Year 4). At Year 4, a significantly greater proportion of eteplirsen-treated patients were still ambulant versus controls (10/12 vs 3/11; p = 0.020). At Year 3, eteplirsen-treated patients had milder NSAA decline than controls (difference in change from baseline of 2.6, 95%CI [-6, 11]), however, the difference was not statistically significant; Year 4 control NSAA data were not available. Conclusion: In this retrospective matched control study, eteplirsen treatment resulted in attenuation of ambulatory decline over a 4-year observation period, supporting long-term benefit in patients with DMD.

scholarly journals Disrupted Calcium Homeostasis in Duchenne Muscular Dystrophy: A Common Mechanism behind Diverse Consequences

2021 ◽  
Vol 22 (20) ◽  
pp. 11040
Author(s):  
Barbara Zabłocka ◽  
Dariusz C. Górecki ◽  
Krzysztof Zabłocki
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Calcium Homeostasis ◽  
Gene Mutations ◽  
Common Mechanism ◽  
Developmental Phase ◽  
Striated Muscles ◽  
Gene Encoding ◽  
Dmd Gene ◽  
The Impact

Duchenne muscular dystrophy (DMD) leads to disability and death in young men. This disease is caused by mutations in the DMD gene encoding diverse isoforms of dystrophin. Loss of full-length dystrophins is both necessary and sufficient for causing degeneration and wasting of striated muscles, neuropsychological impairment, and bone deformities. Among this spectrum of defects, abnormalities of calcium homeostasis are the common dystrophic feature. Given the fundamental role of Ca2+ in all cells, this biochemical alteration might be underlying all the DMD abnormalities. However, its mechanism is not completely understood. While abnormally elevated resting cytosolic Ca2+ concentration is found in all dystrophic cells, the aberrant mechanisms leading to that outcome have cell-specific components. We probe the diverse aspects of calcium response in various affected tissues. In skeletal muscles, cardiomyocytes, and neurons, dystrophin appears to serve as a scaffold for proteins engaged in calcium homeostasis, while its interactions with actin cytoskeleton influence endoplasmic reticulum organisation and motility. However, in myoblasts, lymphocytes, endotheliocytes, and mesenchymal and myogenic cells, calcium abnormalities cannot be clearly attributed to the loss of interaction between dystrophin and the calcium toolbox proteins. Nevertheless, DMD gene mutations in these cells lead to significant defects and the calcium anomalies are a symptom of the early developmental phase of this pathology. As the impaired calcium homeostasis appears to underpin multiple DMD abnormalities, understanding this alteration may lead to the development of new therapies. In fact, it appears possible to mitigate the impact of the abnormal calcium homeostasis and the dystrophic phenotype in the total absence of dystrophin. This opens new treatment avenues for this incurable disease.

scholarly journals PREVALENCE OF ß-THALASSEMIA MUTATIONS AMONG NORTHEASTERN IRANIAN POPULATION AND THEIR IMPACTS ON HEMATOLOGICAL INDICES AND APPLICATION OF PRENATAL DIAGNOSIS, A SEVEN-YEARS STUDY

2018 ◽  
Vol 10 (1) ◽  
pp. e2018042 ◽  
Author(s):  
Mohammad Ehsan Jaripour ◽  
Kourosh Hayatigolkhatmi ◽  
Vahid Iranmanesh ◽  
Farhad Khadivi Zand ◽  
Zahra Badiei ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Los Angeles ◽  
Chorionic Villus ◽  
Amplification Refractory Mutation System ◽  
Chorionic Villus Sampling ◽  
Dot Blot ◽  
Diverse Range ◽  
Hematological Indices ◽  
Arms Pcr ◽  
Significant Difference

Background and objective: ß-thalassemia results from a diverse range of mutations inside the hemoglobin subunit β (HBB) gene. In a study of β-thalassemia carriers and some of their at-risk fetuses in the Khorasan province of Iran we aimed to recognize the most common mutations in the region and to find a possible link between these mutations and some of the relevant hematological indices.Methods: Amplification-refractory mutation system-PCR (ARMS-PCR) was used to detect the typical HBB mutations among 1593 individuals, suspected of having a mutated HBB allele from March/2011 to January/2018. Sanger sequencing of HBB had been performed, where ARMS-PCR was uninformative. In some cases, reverse dot blot was utilized. Analysis of variance was used to compare parametric variables.Results: Among 1273 ß-thalassemia carriers, the prevalence of the mutations were reported as follows: IVS-I-5 (42.03%), IVS-II-1 (11.23%), Codons 8/9 (4.79%), Codon 44 (4.56%), codon 15 (3.53%), Los Angeles (2.91%), Codon 5 (2.75%), IVS-I-110 (2.51%), -88 (2.20%) and other mutations were less than 2% of all of the reported mutations. 644 conceptions were subjected to prenatal diagnosis, using chorionic villus sampling. 118 cases were reported as normal. 352 cases were detected as carriers. 174 cases were diagnosed as affected. There was a significant difference in mean corpuscular volume and hemoglobin A2 levels between the 9 most commonly reported mutation types (p<0.001).Conclusion: This study makes a reliable guide for ß-thalassemia diagnosis in the region. The possibility of a correlation between HBB mutations and hematological indices opens a gate of future investigations.

scholarly journals Unexpected DMD Gene Mutations Detected by CMA and CNV-seq in amniotic Fluid and Aborted Fetus Samples

2021 ◽  
Author(s):  
Qiuhua Wu ◽  
Lihui Yang ◽  
Qiujie Jin ◽  
Rui Wang ◽  
Wen Zhai ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Muscular Dystrophy ◽  
Amniotic Fluid ◽  
Spontaneous Abortion ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Becker Muscular Dystrophy ◽  
Hereditary Diseases ◽  
Muscle Dysfunction ◽  
Dmd Gene

Abstract Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are common X chromosome-linked recessive hereditary diseases. The mechanism is that the exon mutations of anti-myatrophy protein gene (Dystrophin gene) and lead to muscle dysfunction. Prenatal diagnosis can prevent the birth of children with defects and have good clinical significance. Methods: CMA and CNV-seq were used to detect the amniotic fluid after amniocentesis,. CNV-seq was used to detect spontaneous abortion tissue. The DMD gene mutations were found in 6 amniotic fluid samples and one spontaneous abortion sample. DMD gene mutations were confirmed by MLPA and new DMD mutations were found.Results: CMA found DMD mutations :1.Xp21.1, 75.5kb del (E52-53); 2.Xp21.2, 334.92kb dup (E61-79); 3.Xp21.2, 292.25kb dup (E58-74); 4.Xp21.1, 374.20 kb dup (E45-51). CNV-seq found DMD mutations: 5.X p21.2, E64-79 dup; 6.X p21.1, E1-7dup; 7.Xp21.1, E 44-52 del. Conclusions: 4 fetuses harboring DMD gene mutations were found by CMA, 2 fetuses and 1 induced abortion carrying DMD gene mutations was detected by CNV-seq. CMA/CNV-seq jointed with MLPA test can provide more comprehensive evidence for prenatal diagnosis.

Biochemistry, Cytogenetics and DMD Gene Mutations in South Indian Patients with Duchenne Muscular Dystrophy

2017 ◽  
Vol 17 (3) ◽  
pp. 126-134
Author(s):  
A. Meyyazhagan ◽  
N. M. Raman ◽  
M. Easwaran ◽  
B. Balasubramanian ◽  
K. Alagamuthu ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gene Mutations ◽  
Indian Patients ◽  
South Indian ◽  
Dmd Gene

Prenatal diagnosis of Duchenne muscular dystrophy and cytogenetic analysis in 303 Chinese families

2020 ◽  
Author(s):  
Mengmeng Li ◽  
Fengxia Yao ◽  
Na Hao ◽  
Weimin Zhang ◽  
Jing Zhou ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Prenatal Diagnosis ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Pregnant Women ◽  
Gene Mutation ◽  
Trisomy 21 ◽  
Karyotype Analysis ◽  
Chinese Families ◽  
Dmd Gene

Abstract Background: Duchenne muscular dystrophy (DMD) has showed a wide spectrum of mutations in the dystrophin gene including exon deletions, duplications and small mutations. This retrospective study was to supply information of the DMD mutational spectrum in 303 Chinese families and further offer 5-year clinical experience of DMD genetic counselling and prenatal diagnosis.Methods: In this retrospective study, 305 pregnancies in 303 pregnant women who has a birth history of DMD patients underwent prenatal diagnosis using multiplex ligation-dependent probe amplification (MLPA) followed by Sanger sequencing between 2014 and 2018. Karyotype analysis was performed to exclude fetal abnormal karyotype.Results: The detection rate of DMD gene mutation in 303 probands was 97.7% with 7 families having a negative genetic diagnosis. The mutational spectrum comprised of large arrangements in 288/303 (95.0%) and small mutations in 8/303 (2.6%). 204 pregnant women did carrier testing among whom, 108 mothers had the same mutation as family proband. Of the 305 pregnancies underwent prenatal diagnosis, 55 of 173 male fetuses were affected. We also performed karyotype analysis and found 3 abnormal karyotypes of trisomy 21. We even found a fetus with DMD gene mutation and trisomy 21 in a same fetus by further analysis.Conclusions: The distribution and mutation profile of 303 probands and 305 fetuses were demonstrated. Given the large samples provided in this study, the information is essential for genetic counselling and prenatal diagnosis in DMD families in China.

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