scholarly journals Confined placental mosaicism of Duchenne muscular dystrophy: a case report

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Max Winerdal ◽  
Eini Westenius ◽  
Michaela Granfors ◽  
Maria Pettersson ◽  
Erik Iwarsson
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Copy Number ◽  
Chorionic Villus ◽  
Clinical Importance ◽  
Copy Number Variations ◽  
Fragile Sites ◽  
Chorionic Villus Sampling ◽  
Increased Risk ◽  
Placental Mosaicism

Abstract Background Small copy number variations confined to the placenta are extremely rare findings in chorionic villus sampling, nonetheless of great clinical importance. To the best of our knowledge, this is the first reported case of confined placental mosaicism for an intragenic Duchenne muscular dystrophy (DMD) gene deletion. Case presentation We describe a pregnant woman where confined placental mosaicism for an intragenic DMD deletion was detected. She was referred for a chorionic villus sampling due to an increased risk of trisomy 21 derived from combined first trimester screening. Rapid aneuploidy detection showed a male fetus with normal results for chromosomes 13, 18 and 21. A chromosomal microarray demonstrated a deletion of exons 61–62 in the DMD gene in approximately 50% of the cells. A follow-up analysis on amniotic cells showed a normal result for the DMD gene. Hence, confined placental mosaicism was confirmed. Conclusions We propose tissue specific fragile sites as a possible theoretical mechanism for the formation of submicroscopic copy number variations and highlight that the finding of DMD deletion mosaicism in a chorionic villus sample might be isolated to the placenta. Therefore, confirmation by amniocentesis is of crucial clinical importance to avoid misdiagnosis of the fetus.

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 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 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.

Risk of fetal mosaicism when placental mosaicism is diagnosed by chorionic villus sampling

1996 ◽  
Vol 174 (3) ◽  
pp. 850-855 ◽  
Author(s):  
Owen P. Phillips ◽  
Avirachan T. Tharapel ◽  
Jody L. Lerner ◽  
Vicki M. Park ◽  
Stephen S. Wachtel ◽  
...  
Keyword(s):  
Chorionic Villus ◽  
Chorionic Villus Sampling ◽  
Placental Mosaicism

scholarly journals INCREASED NUCHAL TRANSLUCENCY IN A FETUS WITH A NORMAL KARYOTYPE: CASE REPORT

2019 ◽  
Vol 2 (1) ◽  
pp. 59-61
Author(s):  
Cristina Moisei ◽  
Anca Lesnica ◽  
Romina Marina Sima ◽  
Liana Pleș
Keyword(s):  
Chorionic Villus ◽  
Normal Karyotype ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Trisomy 18 ◽  
Trisomy 13 ◽  
Chorionic Villus Sampling ◽  
Increased Risk ◽  
First Trimester Ultrasound ◽  
Increased Nuchal Translucency

Nuchal translucency (NT) is the normal fluid filled subcutaneous space measured at the back of the fetal neck measured in the late first trimester and early second trimester. Nuchal translucency screening can detect approximately 80% of fetuses with Down syndrome and other major aneuploidies with a rate of 5% of false positive results, but the merger of the NT screening with β-hCG and PAPP-A testing increases the detection rate to 90%. We present the case of a fetus with a NT of 49 mm detected at the first trimester ultrasound morphologic exam. The Kryptor test revealed a 1:35 risk for Trisomy 13 and 1:721 for Trisomy 18. We report the case of an investigated pregnancy with a NT of 49 mm detected at the first trimester ultrasound exam, with a risk of 1:35 for Trisomy 13 and 1:721 for Trisomy 18 calculated at the Kryptor test. A chorionic villus sampling was recommended and performed with a result of 46XY normal karyotype. The particularity of this case is represented by the increased nuchal translucency as well as an increased risk for trisomy 13 and 18 in a normal karyotype fetus that had a normal development in the second and third trimester with no pregnancy complications arising.

Vitamin D in the prevention and treatment of comorbid conditions in Duchenne muscular dystrophy

2021 ◽  
Vol 2 (1) ◽  
pp. 38-50
Author(s):  
Tatiana A. Gremiakova ◽  
Vasiliy M. Souslov ◽  
Gulzhan E. Sakbaeva ◽  
Andrey A. Stepanov
Keyword(s):  
Vitamin D ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Steroid Therapy ◽  
Motor Development ◽  
Smooth Muscles ◽  
Comorbid Conditions ◽  
Increased Risk ◽  
Positive Effect ◽  
Tubular Bones

Duchenne muscular dystrophy (DMD) is an X-linked recessive degenerative neuromuscular disorder due to a deficiency of dystrophin protein. This protein is most common in skeletal and cardiac muscles, to a lesser extent in smooth muscles and the brain. With DMD, progressive damage and muscle degeneration, a delay in motor development, and respiratory cardiac disorders are progressing. Patients with DMD have an increased risk of developing osteoporosis, fractures of the tubular bones and vertebrae, and neurocognitive impairment. Vitamin D is recommended prophylactically for DMD since many studies have shown its deficiency. The purpose of this work is to consolidate the literature data on the vitamin D deficiency in DMD patients and its effects on the development of concurrent comorbid conditions of the musculoskeletal, endocrine, and nervous systems. The authors discuss data concerning the appropriate level of vitamin D throughout the life span of DMD has a positive effect on the course of the disease patients’ quality of life ends. Primary clinical outcomes of vitamin D normalization include prevention of the development of osteoporosis (especially after the start of steroid therapy), fractures of the tubular bones and vertebrae, prolonged ability to walk, more effective treatment with bisphosphonates, including a decrease in the number of complications during initial use and lower jaw necrosis, positive effect on the expression of autistic spectrum symptoms. For patients with long-term steroid therapy, metabolic and liver disorders, calcidiol could be used, allowing quick deficiency compensation instead of standard vitamin D preparations.

Increased risk of aneuploidy in women having unsuccessful chorionic villus sampling procedures

1993 ◽  
Vol 100 (9) ◽  
pp. 826-827 ◽  
Author(s):  
Lan E. Donnenfeld ◽  
Ronald J. Librizzi ◽  
Stuart Weiner ◽  
Ronald J. Bolognese
Keyword(s):  
Chorionic Villus ◽  
Chorionic Villus Sampling ◽  
Increased Risk ◽  
Sampling Procedures

scholarly journals FSHD: copy number variations on the theme of muscular dystrophy

2010 ◽  
Vol 191 (6) ◽  
pp. 1049-1060 ◽  
Author(s):  
Daphne Selvaggia Cabianca ◽  
Davide Gabellini
Keyword(s):  
Muscular Dystrophy ◽  
Copy Number ◽  
Phenotypic Diversity ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Copy Number Variations ◽  
Common Source ◽  
Epigenetic Events ◽  
Rate Of Progression ◽  
Chromosomal Architecture ◽  
Severity Of The Disease

In humans, copy number variations (CNVs) are a common source of phenotypic diversity and disease susceptibility. Facioscapulohumeral muscular dystrophy (FSHD) is an important genetic disease caused by CNVs. It is an autosomal-dominant myopathy caused by a reduction in the copy number of the D4Z4 macrosatellite repeat located at chromosome 4q35. Interestingly, the reduction of D4Z4 copy number is not sufficient by itself to cause FSHD. A number of epigenetic events appear to affect the severity of the disease, its rate of progression, and the distribution of muscle weakness. Indeed, recent findings suggest that virtually all levels of epigenetic regulation, from DNA methylation to higher order chromosomal architecture, are altered at the disease locus, causing the de-regulation of 4q35 gene expression and ultimately FSHD.

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