Dataset Information

Experiences of Women Who Have Had Carrier Testing for Duchenne Muscular Dystrophy and Becker Muscular Dystrophy During Adolescence.

ABSTRACT: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive degenerative muscular conditions. Carrier testing is available to at-risk females. Though carrier testing is often offered to adolescent females, it raises ethical issues related to autonomy. This study aimed to address the impact of DMD/BMD carrier testing during adolescence, to elucidate what motivates adolescents to seek testing, and to assess the carrier testing experience. Retrospective semi-structured telephone interviews were conducted with 12 women out of 28 initially contacted. Data were coded using thematic analysis. For most (8/12) participants, discovering their carrier status during adolescence appeared to have helped alleviate uncertainty. The majority (9/12) of participants felt that they had made an autonomous decision and most (10/12) seemed to have adjusted well to their test result. Reproductive factors were framed as having been a key motivator prior to testing. However, following testing, participants' views on prenatal diagnosis seemed more closely linked to their lived experience than to their test result. Just over half (7/12) the participants reported having not had the opportunity for genetic counseling prior to testing and after receiving their result, an issue that warrants further consideration.

SUBMITTER: Fraser HG

PROVIDER: S-EPMC6209047 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Experiences of Women Who Have Had Carrier Testing for Duchenne Muscular Dystrophy and Becker Muscular Dystrophy During Adolescence.

Fraser Harry G HG Redmond Rebecca Z RZ Scotcher Diana F DF

Journal of genetic counseling 20180704 6

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive degenerative muscular conditions. Carrier testing is available to at-risk females. Though carrier testing is often offered to adolescent females, it raises ethical issues related to autonomy. This study aimed to address the impact of DMD/BMD carrier testing during adolescence, to elucidate what motivates adolescents to seek testing, and to assess the carrier testing experience. Retrospective semi-structu ...[more]

PMID: 29974322

Similar Datasets

Project description:BackgroundDuchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are characterized by muscle wasting leading to loss of ambulation in the first or third decade, respectively. In DMD, the lack of dystrophin hampers connections between intracellular cytoskeleton and cell membrane leading to repeated cycles of necrosis and regeneration associated with inflammation and loss of muscle ordered structure. BMD has a similar muscle phenotype but milder. Here, we address the question whether proteins at variance in BMD compared with DMD contribute to the milder phenotype in BMD, thus identifying a specific signature to be targeted for DMD treatment.MethodsProteins extracted from skeletal muscle from DMD/BMD patients and young healthy subjects were either reduced and solubilized prior two-dimensional difference in gel electrophoresis/mass spectrometry differential analysis or tryptic digested prior label-free liquid chromatography with tandem mass spectrometry. Statistical analyses of proteins and peptides were performed by DeCyder and Perseus software and protein validation and verification by immunoblotting.ResultsProteomic results indicate minor changes in the extracellular matrix (ECM) protein composition in BMD muscles with retention of mechanotransduction signalling, reduced changes in cytoskeletal and contractile proteins. Conversely, in DMD patients, increased levels of several ECM cytoskeletal and contractile proteins were observed whereas some proteins of fast fibres and of Z-disc decreased. Detyrosinated alpha-tubulin was unchanged in BMD and increased in DMD although neuronal nitric oxide synthase was unchanged in BMD and greatly reduced in DMD. Metabolically, the tissue is characterized by a decrement of anaerobic metabolism both in DMD and BMD compared with controls, with increased levels of the glycogen metabolic pathway in BMD. Oxidative metabolism is severely compromised in DMD with impairment of malate shuttle; conversely, it is active in BMD supporting the tricarboxylic acid cycle and respiratory chain. Adipogenesis characterizes DMD, whereas proteins involved in fatty acids beta-oxidation are increased in BMD. Proteins involved in protein/amino acid metabolism, cell development, calcium handling, endoplasmic reticulum/sarcoplasmic reticulum stress response, and inflammation/immune response were increased in DMD. Both disorders are characterized by the impairment of N-linked protein glycosylation in the endoplasmic reticulum. Authophagy was decreased in DMD whereas it was retained in BMD.ConclusionsThe mechanosensing and metabolic disruption are central nodes of DMD/BMD phenotypes. The ECM proteome composition and the metabolic rewiring in BMD lead to preservation of energy levels supporting autophagy and cell renewal, thus promoting the retention of muscle function. Conversely, DMD patients are characterized by extracellular and cytoskeletal protein dysregulation and by metabolic restriction at the level of ?-ketoglutarate leading to shortage of glutamate-derived molecules that over time triggers lipogenesis and lipotoxicity.

Project description:BackgroundThe social context of rare disease research is changing, with increased community engagement around drug development and clinical trials. This engagement may benefit patients and families but may also lead to heightened trial expectations and therapeutic misconception. Clinical investigators are also susceptible to harboring high expectations. Little is known about parental motivations and expectations for clinical trials for rare pediatric disorders.PurposeWe describe the experience of parents and clinical investigators involved in a phase II clinical trial for Duchenne and Becker muscular dystrophy: their expectations, hopes, motivations, and reactions to the termination of the trial.MethodsThis qualitative study was based on interviews with clinical investigators and parents of sons with Duchenne and Becker muscular dystrophy (DBMD) who participated in the phase IIa or IIb ataluren clinical trial in the United States. Interviews were transcribed and coded for thematic analysis.ResultsParticipants were 12 parents of affected boys receiving active drug and 9 clinical investigators. High trial expectations of direct benefit were reported by parents and many clinicians. Investigators described monitoring and managing parents' expectations; several worried about their own involvement in increasing parents' expectations. Most parents were able to differentiate their expectations from their optimistic hopes for a cure. Parents' expectations arose from other parents, advocacy organizations, and the sponsor. All parents reported some degree of clinical benefit to their children. Secondary benefits were hopefulness and powerful feelings associated with active efforts to affect the disease course. Parents and clinical investigators reported strong, close relationships that were mutually important. Parents and clinicians felt valued by the sponsor for the majority of the trial. When the trial abruptly stopped, they described loss of engagement, distress, and feeling unprepared for the possibility of trial termination.LimitationsThis was a retrospective study of one clinical trial. We were unable to recruit participants whose children received placebo. The interviews occurred during a time of significant uncertainty and distress for many of the participants.ConclusionThis pilot study reflects complex outcomes of strong community engagement. The findings highlight a need for renewed education about, and support for, clinical trial termination and loss of drug access. The primary positive outcome was demonstration of strong relationships among committed parents and study teams. These relationships were highly valued by both parties and may suggest an ideal intervention opportunity for efforts to improve psychological well-being. A negative outcome attributed, in part, to community engagement was inappropriately high trial expectations. More optimistically, high expectations were attributed, in part, to the importance of hope and powerful feelings associated with active efforts to affect the disease course.

Project description:BackgroundDuchenne Muscular Dystrophy (DMD) is the most common muscle disease in children, and there are no effective therapies for DMD or Becker Muscular Dystrophy (BMD). Currently, targeted gene therapy treatments have emerged. As a result, genetic diagnosis is the basis of treatment. In addition, genetic and prenatal diagnosis significantly reduces their incidence rates. This study combines the application of multiplex ligation-dependent probe amplification technology (MLPA) and "next-generation" sequencing technology (NGS) as the most economical and efficient method of diagnosis. Therefore, in the diagnosis of DMD/BMD, patients' MLPA data are first used to detect DMD gene deletions or duplications, and NGS and Sanger sequencing are then applied to exclude MLPA-negative samples. Meanwhile, polymerase chain reaction (PCR) is used to detect single exon deletions to exclude false-positives in MLPA caused by point mutations.MethodsIn this study, we recruited 1051 proband families of DMD from 2016 to 2018 and had access to information that could identify individual participants during or after data collection. Patients who were diagnosed with DMD were first tested by MLPA. MLPA results with single exon deletions were validated with PCR amplification and Sanger sequencing. The negative results of MLPA were further analysed with NGS and validated by Sanger sequencing. For novel missense mutations, phenotype-genotype correlations were analysed using PolyPhen2 and mutation taster. All methods were performed in accordance with the relevant guidelines and regulations.ResultsDMD mutations were identified in 1029 families (97.91%, 1029/1051). Large deletions, duplications, and small mutations accounted for 70.41% (740/1051), 8.28% (87/1051), and 19.12% (201/1051) of all cases, respectively. There were 205 small mutation types, 53 of which were novel. The rate of de novo mutations was 39.45% (187/474) and was higher in large duplications (49.53%, 157/317). Among 68 asymptomatic patients (< 3 years old) with unexplained persistent hyperCKaemia upon conventional physical examination, 63 were diagnosed as DMD/BMD according to genetic diagnosis.ConclusionOur results expand the spectrum of DMD mutations, which could contribute to the treatment of DMD/BMD and provide an effective diagnosis method. Thus, the combination of MLPA, NGS and Sanger sequencing is of great significance for family analysis, gene diagnosis and gene therapy.

Dataset Information

Experiences of Women Who Have Had Carrier Testing for Duchenne Muscular Dystrophy and Becker Muscular Dystrophy During Adolescence.

Publications

Experiences of Women Who Have Had Carrier Testing for Duchenne Muscular Dystrophy and Becker Muscular Dystrophy During Adolescence.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets