Correlations between individual clinical manifestations and CTG repeat amplification in myotonic dystrophy

Marchini, C.; Lonigro, Renata; Verriello, Lorenzo; Pellizzari, Lucia; Bergonzi, P; Damante, Giuseppe

doi:10.1034/j.1399-0004.2000.570112.x

Cited by 89 publications

(72 citation statements)

References 50 publications

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“…The molecular tests diagnose patients with 100% accuracy, without overlap between normal alleles and expanded full penetrance alleles. In contrast, the clinical manifestations and their severity broadly correlate with the size of CTG repeat expansion [15][16][17], but findings vary greatly between patients.…”

Section: Discussionmentioning

confidence: 87%

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans

Kim

et al. 2008

Ann Lab Med

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Section: Discussionmentioning

confidence: 87%

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans

Kim

et al. 2008

Ann Lab Med

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“…7 It is therefore possible that variant repeats might mediate an altered pathology through other mechanisms, such as changing the methylation status of the region up and/or down of the repeat, modulating chromatin structure and the nucleosome assembly. 20,21 A recent paper, reported indeed that the presence of CCG/CTC/ CGG interruptions at the 3′ end of the CTG array is associated with a highly polarized pattern of CpG methylation at the DM1 locus involving regions downstream of the CTG array. 22 Another important issue is the contribution of unusual DMPK alleles to the DM1 clinical picture.…”

Section: Discussionmentioning

confidence: 99%

“…The number of DM1 individuals with interruptions described is however limited and their phenotype range from a complex neurological involvement to the absence of muscular dystrophy associated with a late age of onset. 5,21 Further genetic studies are necessary to understand the possibly modifying effects of these interruptions and to provide patients with improved prognostic information associated with variant DMPK expansions. Figure 2 Long range-PCR, using primers EX15-Fw and DMK1111-Rv, 9 and Southern blot analysis of members belonging to families A, B and C. Pedigrees with estimated sizes of CTG expansions in the analyzed family members are added to the top of the figure.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of 5′ CCG interruptions in complex DMPK expanded alleles

et al. 2016

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Myotonic dystrophy type 1 is a multisystemic autosomal dominant disorder caused by the expansion of (CTG) n triplets in the 3'UTR of the DMPK gene, on chromosome 19q13.3. In the last years, few DM1 patients with different patterns of CCG/CTC interruptions at the 3′ end of the DMPK expanded tract have been described. However, the role of these interruptions in DM1 pathogenesis is still unclear. To study the frequency, stability and the structure of DMPK variant expanded alleles in the Italian population, we have re-evaluated 254 Italian DM1 patients using triplet-primed PCR (TP-PCR), at both the 3′ and 5′ ends of the CTG expansion. In addition, three DM1 families were also investigated in order to analyze the intergenerational stability of the interrupted DMPK alleles. Fourteen DM1 patients showed a TP-PCR electrophoretic profile indicating CCG/CTC interruptions within the CTG expansion. Interestingly, interruptions have been detected and, for the first time, sequenced at the 5′ end of the CTG array. Analysis of five intergenerational transmissions revealed a substantial intrafamilial stability of the DM1 mutation among relatives. Our results support the hypothesis that CCG/CTC interruptions within the DMPK expanded alleles have a stabilizing effect on the mutational dynamics and can modulate the severity of symptoms in DM1 patients.

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“…The number of CTG repeats correlates broadly with the overall severity of the disease, but the correlation between the size of the CTG repeat sequence and individual clinical manifestations still needs to be elucidated. 1 DM can be congenital and can appear in childhood or later in life (adult or classical type). The cardinal symptoms are weak muscles, especially in the face, neck, hands, and feet, but smooth muscles are also affected.…”

mentioning

confidence: 99%

Orofacial dysfunction in children and adolescents with myotonic dystrophy

Sjögreen¹,

Engvall²,

Ekström

et al. 2006

Develop Med Child Neuro

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Myotonic dystrophy (DM) is a neuromuscular disorder caused by an expansion of a CTG repeat sequence on chromosome 19q13. The aim of the present study was to describe the characteristics and prevalence of oral motor dysfunction in a cohort of children and adolescents with DM and to correlate different aspects of oral motor function with the type of DM and sex. Fifty-six individuals with DM (30 males, 26 females; median age 13y 2mo; range 2y 6mo-21y 5mo) were compared with healthy controls. They were divided into four subgroups: severe congenital DM (n=18); mild congenital DM (n=18); childhood DM (n=18); and classical DM (n=2). A speechlanguage pathologist assessed different variables of oral motor function, intelligibility, and lip force. The families used a questionnaire to report on eating difficulties and drooling. All individuals with DM had impaired facial expression. Intelligibility was moderately or severely reduced in 30 patients (60%), excluding six patients without speech. Most had a moderate or severe impairment of lip motility (76.0%), tongue motility (52.2%), and lip force (69.2%), causing deviant production of bilabial and dental consonants. The families reported problems with eating (51.9%) and drooling (37.0%). Oral motor dysfunction was most prominent in congenital DM, and males were more affected than females.Myotonic dystrophy (DM) is a slowly progressive neuromuscular disorder with autosomal dominant inheritance. It is caused by an expansion of a CTG repeat sequence (trinucleotide expansion) on chromosome 19q13. The number of CTG repeats correlates broadly with the overall severity of the disease, but the correlation between the size of the CTG repeat sequence and individual clinical manifestations still needs to be elucidated. 1 DM can be congenital and can appear in childhood or later in life (adult or classical type). The cardinal symptoms are weak muscles, especially in the face, neck, hands, and feet, but smooth muscles are also affected. 2 Myotonia is a common feature in adults with DM but this can also be seen in children. [2][3][4][5] Most individuals with the congenital or childhood type have learning disability* and there are an increased number of children and adolescents with DM who have a neuropsychiatric disorder in comparison with the prevalence in the general population. [4][5][6][7] Newborn infants with the congenital form of DM generally have profound difficulties with sucking and breathing because of neonatal hypotonia. Polyhydramnios during pregnancy, caused by poor fetal swallowing, is often noted. 2,4,5 Adults with DM commonly develop flaccid dysarthria with indistinct articulation and hypernasal speech caused by velopharyngeal impairment. [8][9][10][11] The speech characteristics of children and adolescents with DM have not been described previously in any detail. Although orofacial weakness is a characteristic symptom in congenital and childhood DM, 2,4,5 research into the consequences for feeding in infancy, chewing, swallowing, and speech is very limited. Different as...

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Correlations between individual clinical manifestations and CTG repeat amplification in myotonic dystrophy

Cited by 89 publications

References 50 publications

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans

Identification and characterization of 5′ CCG interruptions in complex DMPK expanded alleles

Orofacial dysfunction in children and adolescents with myotonic dystrophy

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