Prenatal diagnosis in myotonic dystrophy type 1. Thirteen years of experience: implications for reproductive counselling in DM1 families

Martorell, Loreto; Cobo, Ana Maria; Baiget, Montserrat; Naudó, Montserrat; Poza, Juan José; Parra, Johanna

doi:10.1002/pd.1627

Cited by 38 publications

(27 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A recent study demonstrated that the GAA⅐TTC repeat observed in Friedreich ataxia and the CTG repeat characteristic of myotonic dystrophy are unstable during passage of human iPSCs or human embryonic stem cells (26,28). Both repeat expansions are very large (ϳ100 to ϳ1000 bp) in the noncoding regions, and instability with maternal transmission of the expanded allele has been described (44,45). The mismatch repair enzyme MSH2, which is up-regulated during reprogramming, has been implicated in GAA⅐TTC repeat instability.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Aggregation of Androgen Receptor in Induced Pluripotent Stem Cell-derived Neurons from Spinal and Bulbar Muscular Atrophy

Nihei

Ito

Okada

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Induced pluripotent stem cells (iPSCs) are a novel technology for modeling neurodegeneration. Results: We established spinal and bulbar muscular atrophy (SBMA)-derived iPSCs and confirmed motor neuron differentiation. Aggregation of androgen receptor in SBMA-iPSC-derived neurons is enhanced by DHT and inhibited by 17-AAG. Conclusion: SBMA-iPSCs show disease-specific biochemical features. Significance: Using SBMA-iPSCs is an innovative strategy for studying polyglutamine diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhanced Aggregation of Androgen Receptor in Induced Pluripotent Stem Cell-derived Neurons from Spinal and Bulbar Muscular Atrophy

Nihei

Ito

Okada

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…However, it is important to note that more than half of the affected mothers do not carry a diagnosis of DM1 because their condition has gone unrecognized, 31 or has not generated any symptoms. 32 Later in childhood, individuals with CDM exhibit delayed motor milestones and a range of learning disabilities, including autism spectrum disorder. 29, 33 Oropharyngeal weakness is prominent, often producing a characteristic tented appearance of the upper lip, facial diplegia, marked dysarthria, and greater impairment of expressive than receptive communication.…”

Section: Congenital Dm1 (Cdm)mentioning

confidence: 99%

Myotonic Dystrophy

2014

View full text Add to dashboard Cite

Myotonic dystrophy (dystrophia myotonica, DM) is one of the most common lethal monogenic disorders in populations of European descent. Myotonic dystrophy type 1 (DM1) was first described over a century ago. DM1 is caused by expansion of a CTG triplet repeat in the 3' non-coding region of DMPK, the gene encoding the DM protein kinase. More recently a second form of the disease, myotonic dystrophy type 2 (DM2) was recognized, which results from repeat expansion in a different gene. The DM2 expansion involves a CCTG repeat in the first intron of Zinc Finger 9 (ZNF9). Both disorders have autosomal dominant inheritance and multisystem features, including myotonic myopathy, cataract, and cardiac conduction disease. Studies suggest that the shared clinical features of DM1 and DM2 involve a novel genetic mechanism in which repetitive RNA exerts a toxic effect. The RNA toxicity stems from the expanded repeat in the transcripts from the mutant DM alleles. This chapter will review the clinical presentation and pathophysiology of DM, and discuss current management and future potential for developing targeted therapies.

show abstract

“…In the case of autosomal dominant myotonic dystrophy, TRD has been reported in live-born offspring from affected female parents but not affected male parents. [3][4][5] When looking at meioses from unaffected parents heterozygote for different repeat lengths (non-disease causing) at the DM locus, there was a significant distortion in favour of transmission of the larger allele in males. 6 In contrast, no TRD was determined for any allele length when sperm from heterozygous unaffected donors were analysed 7 or when pre-natal diagnoses were analysed from either affected mothers or fathers.…”

Section: Introductionmentioning

confidence: 99%

Is there a Mendelian transmission ratio distortion of the c.429_452dup(24bp) polyalanine tract ARX mutation?

et al. 2012

View full text Add to dashboard Cite

Intellectual disability is common. Aristaless-related homeobox (ARX) gene is one of the most frequently mutated and pleiotropic genes, implicated in 10 different phenotypes. More than half of B100 reported cases with ARX mutations are due to a recurrent duplication of 24 bp, c.429_452dup, which leads to polyalanine tract expansion. The excess of affected males among the offspring of the obligate carrier females raised the possibility of transmission ratio distortion for the c.429_452dup mutation. We found a significant deviation from the expected Mendelian 1:1 ratio of transmission in favour of the c.429_452dup ARX mutation. We hypothesise that the preferential transmission of the c.429_452dup mutation may be due to asymmetry of meiosis in the oocyte. Our findings may have implications for genetic counselling of families segregating the c.429_452dup mutation and allude to putative role of ARX in oocyte biology.

show abstract

Prenatal diagnosis in myotonic dystrophy type 1. Thirteen years of experience: implications for reproductive counselling in DM1 families

Cited by 38 publications

References 30 publications

Enhanced Aggregation of Androgen Receptor in Induced Pluripotent Stem Cell-derived Neurons from Spinal and Bulbar Muscular Atrophy

Enhanced Aggregation of Androgen Receptor in Induced Pluripotent Stem Cell-derived Neurons from Spinal and Bulbar Muscular Atrophy

Myotonic Dystrophy

Is there a Mendelian transmission ratio distortion of the c.429_452dup(24bp) polyalanine tract ARX mutation?

Contact Info

Product

Resources

About