Cytosine-thymine-guanine Repeat Research Articles

Hypogammaglobulinemia and infection risk in myotonic dystrophy type 1.

Hypogammaglobulinemia is a common yet under-recognized feature of myotonic dystrophy type 1 (DM1). The aims of our study were to determine the frequency of immunoglobulin G (IgG) deficiency in our cohort, to examine the association between immunoglobulin levels and cytosine-thymine-guanine (CTG) repeat length in the DMPK gene, and to assess whether IgG levels are associated with an increased risk of infection in DM1 patients. We conducted a single-center, retrospective cross-sectional study of 65 adult patients with DM1 who presented to the Neuromuscular Clinic at Concord Repatriation General Hospital, Sydney, Australia, between January 2002 and January 2022. We systematically collected and analyzed clinical, laboratory, and genetic data for all patients with available serum electrophoresis and/or IgG level results. Forty-one percent of DM1 patients had IgG deficiency despite normal lymphocyte counts, IgA, IgM, and albumin levels. There was an association between CTG repeat expansion size and the degree of IgG deficiency (F = 6.3, p = .02). There was no association between IgG deficiency and frequency of infection in this group (p = .428). IgG deficiency is a frequent occurrence in DM1 patients and is associated with CTG repeat expansion size. Whether hypogammaglobulinemia is associated with increased infection risk in DM1 is unclear. A prospective multicenter cohort study is needed to evaluate this.

Clinical and genetic characteristics of childhood-onset myotonic dystrophy.

Myotonic dystrophy type 1 (DM1) is caused by a CTG (cytosine-thymine-guanine) trinucleotide repeat expansion. Congenital DM (CDM) presents in the first month of life, whereas individuals with infantile and juvenile DM1 have later onset of symptoms. We performed a retrospective chart review of patients with childhood-onset DM1 seen at one of three locations in Dallas, Texas between 1990 and 2018. Symptoms, disease course, cognitive features, and family history were reviewed. Seventy-four patients were included; CDM was diagnosed in 52 patients. There was maternal inheritance in 74% of patients. CTG repeat number ranged from 143 to 2300. Neuropsychiatric and cognitive deficits were common. Over half of the patients had GI disturbances, and orthopedic complications were common. Myotonic dystrophy type 1 in children requires a multidisciplinary approach to management. Presenting symptoms vary, and repeat expansion size does not necessarily directly relate to severity of symptoms. A consensus for outcome measures is required.

Genotype-phenotype correlations in pediatric patients with myotonic dystrophy type 1.

PurposeMyotonic dystrophy, also known as dystrophia myotonica (DM), is an autosomal dominant disorder with 2 genetically distinct forms. DM type 1 (DM1) is the more common form and is caused by abnormal expansion of cytosine/thymine/guanine (CTG) repeats in the DM protein kinase (DMPK) gene. Our study aimed to determine whether the age of onset is correlated with CTG repeat length in a population of pediatric patients with DM1.MethodsWe retrospectively identified 30 pediatric patients with DM1 that underwent DMPK testing, of which the clinical data of 17 was sufficient. The cohort was divided into 2 subgroups based on the clinical phenotype (congenital-onset vs. late-onset) and number of CTG repeats (<1,000 vs. ≥1,000).ResultsWe found no significant difference between the age of onset and CTG repeat length in our pediatric patient population. Based on clinical subgrouping, we found that the congenital-onset subgroup was statistically different with respect to several variables, including prematurity, rate of admission to neonatal intensive care unit, need for respiratory support at birth, hypotonia, dysphagia, ventilator dependence, and functional status on last visit, compared to the late-onset subgroup. Based on genetic subgrouping, we found a single variable (poor feeding in neonate) that was significantly different in the large CTG subgroup than that in the small CTG subgroup.ConclusionClinical variables exhibiting statistically significant differences between the subgroups should be focused on prognosis and designing tailored management approaches for the patients; our findings will contribute to achieve this important goal for treating patients with DM1.

Genome Therapy of Myotonic Dystrophy Type 1 iPS Cells for Development of Autologous Stem Cell Therapy

Myotonic dystrophy type 1 (DM1) is caused by expanded Cytosine-Thymine-Guanine (CTG) repeats in the 3'-untranslated region (3' UTR) of the Dystrophia myotonica protein kinase (DMPK) gene, for which there is no effective therapy. The objective of this study is to develop genome therapy in human DM1 induced pluripotent stem (iPS) cells to eliminate mutant transcripts and reverse the phenotypes for developing autologous stem cell therapy. The general approach involves targeted insertion of polyA signals (PASs) upstream of DMPK CTG repeats, which will lead to premature termination of transcription and elimination of toxic mutant transcripts. Insertion of PASs was mediated by homologous recombination triggered by site-specific transcription activator-like effector nuclease (TALEN)-induced double-strand break. We found genome-treated DM1 iPS cells continue to maintain pluripotency. The insertion of PASs led to elimination of mutant transcripts and complete disappearance of nuclear RNA foci and reversal of aberrant splicing in linear-differentiated neural stem cells, cardiomyocytes, and teratoma tissues. In conclusion, genome therapy by insertion of PASs upstream of the expanded DMPK CTG repeats prevented the production of toxic mutant transcripts and reversal of phenotypes in DM1 iPS cells and their progeny. These genetically-treated iPS cells will have broad clinical application in developing autologous stem cell therapy for DM1.

Myotonic Dystrophy Type 1 with Syringomyelia in a Young Patient

Myotonic Dystrophy Type 1 with Syringomyelia in a Young Patient

Modelling and inference reveal nonlinear length-dependent suppression of somatic instability for small disease associated alleles in myotonic dystrophy type 1 and Huntington disease

More than 20 human genetic diseases are associated with inheriting an unstable expanded DNA simple sequence tandem repeat, for example, CTG (cytosine-thymine-guanine) repeats in myotonic dystrophy type 1 (DM1) and CAG (cytosine-adenine-guanine) repeats in Huntington disease (HD). These sequences mutate by changing the number of repeats not just between generations, but also during the lifetime of affected individuals. Levels of somatic instability contribute to disease onset and progression but as changes are tissue-specific, age- and repeat length-dependent, interpretation of the level of somatic instability in an individual is confounded by these considerations. Mathematical models, fitted to CTG repeat length distributions derived from blood DNA, from a large cohort of DM1-affected or at risk individuals, have recently been used to quantify inherited repeat lengths and mutation rates. Taking into account age, the estimated mutation rates are lower than predicted among individuals with small alleles (inherited repeat lengths less than 100 CTGs), suggesting that these rates may be suppressed at the lower end of the disease-causing range. In this study, we propose that a length-specific effect operates within this range and tested this hypothesis using a model comparison approach. To calibrate the extended model, we used data derived from blood DNA from DM1 individuals and, for the first time, buccal DNA from HD individuals. In a novel application of this extended model, we identified individuals whose effective repeat length, with regards to somatic instability, is less than their actual repeat length. A plausible explanation for this distinction is that the expanded repeat tract is compromised by interruptions or other unusual features. We quantified effective length for a large cohort of DM1 individuals and showed that effective length better predicts age of onset than inherited repeat length, thus improving the genotype-phenotype correlation. Under the extended model, we removed some of the bias in mutation rates making them less length-dependent. Consequently, rates adjusted in this way will be better suited as quantitative traits to investigate cis- or trans-acting modifiers of somatic mosaicism, disease onset and progression.

Genetics correlates with lung function and nocturnal ventilation in myotonic dystrophy

Dystrophia myotonica (DM) is the most frequent adult-onset muscular dystrophy. Type 1 is caused by the cytosine-thymine-guanine (CTG) repeat expansion in the DM protein kinase gene. Respiratory muscle weakness and altered central ventilatory control lead to hypercapnia and lung volume restriction. This study aims to review the respiratory involvement in DM patients and study its relation with genetics. Retrospective study of patients with DM referred for respiratory assessment was made. Noninvasive ventilation (NIV) was considered to daytime hypercapnia or symptoms of nocturnal hypoventilation. Forty-two consecutive patients (37.9 ± 13.6 years) were evaluated. Mean CTG length was 642.8 ± 439.2 repeats. In the first evaluation, mean forced vital capacity (FVC) was 74.4 ± 20.2 %, maximal expiratory pressure (MEP) 35 ± 16 %, maximal inspiratory pressure 52 ± 23 %, peak cough flow (PCF) 327.3 ± 97.7 L/min, arterial pressure of oxygen 79.7 ± 11.3 mmHg, arterial pressure of carbon dioxide 45.5 ± 6.2 mmHg, overnight minimal peripheral oxygen saturation (SpO2) 79.6 ± 11.6 %, and apnea-hypopnea index 13.9 ± 9.9. CTG length was found to be related with MEP (r = -0.67; p = 0.001) and SpO2 (r = -0.37; p = 0.039). NIV was started in 25 patients. Ventilated patients had lower FVC (2.19 to 3.21 L; p < 0.001) and PCF (285.3 to 388.5 L/min; p = 0.003) and more CTG repeats (826.6 to 388.5 repeats; p = 0.02). NIV compliance was poor in seven patients (28 %) and related with hypercapnia (r = 0.87; p = 0.002) and inspiratory positive airway pressure setting (r = 0.65; p = 0.009). Ventilation improved symptoms and nocturnal hypoventilation. Comparing the first and last evaluations, only PCF was significantly lower (275.0 to 310.8 L/min; p = 0.019). Ventilatory insufficiency is very common in patients with DM and CTG length may be useful to predict it. Prolonged NIV improves symptoms, nocturnal hypoventilation and maintains daily blood gases. Routine evaluation of PCF should not be forgotten and assisted coughing training provided.

Ocular motor function in relation to gross motor function in congenital and childhood myotonic dystrophy type 1

To assess ocular motor function in congenital and childhood myotonic dystrophy type 1 (DM1) and correlate the results with cytosine-thymine-guanine (CTG) repeat size, severity of the disease, myotonia and skeletal muscle function. A cross-sectional investigation into strabismus, versions/ductions, saccades, smooth pursuit movements and ptosis was performed on 49 individuals with a confirmed diagnosis of DM1, all diagnosed at <18 years of age and with >40 CTG expansion repeats. The results were correlated with myotonia as well as Hammersmith motor ability scale (HMA). In addition, the ocular results were compared to results from an age and- sex-matched control group. Ocular motor abnormalities were seen in 82%; the most frequent findings were altered conjugate eye movements and 'pseudoptosis' while blepharoptosis was rare. Strabismus was most common in the severe congenital subgroup, with a frequency 14 times higher than in the control group. Positive correlations were seen between CTG repeat size and affected eyelids, and between myotonia and affected eyelids; both these findings were most prominent in the mild congenital group. CTG repeat size was also correlated with version/duction defects, and most obviously in the childhood group. Low HMA scores were associated with high occurrence of strabismus and version/duction defects. Abnormalities of ocular motor function are frequently present. CTG repeat size correlates positively with altered versions/ductions and eyelid pathology. Gross motor dysfunction correlates with strabismus and defect versions/ductions, and eyelid pathology indicates involvement of myotonia.

Survival and CTG repeat expansion in adults with myotonic dystrophy type 1

An association is observed between the severity of myotonic dystrophy type 1 (DM1) and the genetic abnormality of cytosine-thymine-guanine (CTG) repeat expansion. It is unknown whether an association exists between survival and CTG repeat expansion. In an adult 406-patient DM1 cohort, the phenotype, including survival age, was evaluated in relation to CTG repeat expansion. At study entry, age was 42 ± 12 (range 18-78) years, with a CTG repeat length of 629 ± 386 (range 54-1965). An inverse correlation was observed between CTG repeat length and the age at onset and younger DM1 phenotype. Over a follow-up of 9.2 ± 3.1 years, 118 (29.1%) patients died, including 60 of neuromuscular respiratory failure, 41 of cardiac causes, and 17 of non-neuromuscular, non-cardiac causes. There was an inverse relationship between all-cause survival and CTG length (relative risk 5.4 per log repeat, 95% confidence interval 2.9-10.2, P < 0.001). The data demonstrate a genotype-mortality association in DM1.

Increased temporal dispersion of myocardial repolarization in myotonic dystrophy Type 1: Beyond the cardiac conduction system

Background and objectivesThe most frequently mechanism underlying sudden cardiac death in myotonic dystrophy type 1 (DM1) is bradyarrhythmias due to cardiac conduction abnormalities. However the risk of ventricular tachyarrhythmias remains a concern in clinical management as well as in its determinant. We therefore assessed autonomic nervous system activity aiming to disclose differences in the QT variability index (QTVI)—a marker of temporal myocardial repolarization lability—between DM1 patients and healthy controls. We also investigated the possible differences within DM1 patients by subdividing them according either to the presence of first degree atrioventricular block (1st AVB) or to the cytosine–thymine–guanine (CTG) repeat expansion size. MethodsSixty-two DM1 patients and 20 healthy subjects underwent neurological and cardiological examinations, the latter including ECG, echocardiography and 24-hour Holter monitoring. All underwent a 5-minute ECG recording to assess heart rate variability power spectral components, and the QTVI values. ResultsPower spectral data, namely total power, low frequency power and high frequency power, were lower, whereas QTVI values were higher in DM1 patients than in controls (p<.0001). Higher QTVI values were found in DM1 subgroups with 1st AVB (p=.009) and more than 500 CTG repeat (p=.014) with respect to DM1 patients without 1st AVB and CTG<500. Spectral data did not significantly differ. At multivariable analysis, QTVI and age were independently associated with PR interval and CTG repeat. ConclusionsThe increased values of QTVI argue in favour of an important heart involvement extending beyond the conduction system. Whether QTVI could be useful in predicting clinical course of DM1 clearly requires larger prospective studies.

CTG repeat lengths of the DMPK gene in myotonic dystrophy patients compared to healthy controls in Thailand

Myotonic dystrophy (DM) is frequently associated with large expansions of the cytosine–thymine–guanine (CTG) repeat in the myotonic dystrophy protein kinase gene ( DMPK). The frequency of distribution of the CTG repeat length in normal alleles of several populations is well correlated with the prevalence of DM. Therefore, we studied the CTG repeat length of the DMPK gene in DM patients and controls in Thailand. Only seven typical patients with DM from six unrelated families were identified, all with large pathological CTG repeat expansions (>400 repeats) in the DMPK gene. Only 2.75% of controls had normal CTG repeat alleles >18 repeats. The frequency distribution of the CTG-repeat alleles in the normal Thai population is similar to that of the Taiwanese population (χ 2 with Yates correction = 1.393; p = 0.2379). These data suggest that the incidence of DM might be rare in Thailand, where the risk of developing DM is possibly similar to that in Taiwan.

Visual Function in Congenital and Childhood Myotonic Dystrophy Type 1

To investigate visual function in a group of individuals with congenital and childhood myotonic dystrophy type 1 (DM1), to correlate the results to the size of the cytosine-thymine-guanine (CTG) repeat expansion and the onset form, and to compare the results with those of a control group. Cross-sectional study with age- and gender-matched control groups. Forty-nine individuals with severe and mild congenital and childhood DM1 and controls matched for age and gender. The ophthalmologic examination included best-corrected visual acuity (BCVA), refraction, slit-lamp biomicroscopy, indirect ophthalmoscopy, and flash visual evoked potentials (VEPs). Visual acuity, refractive error, pathology of lens, fundus, and VEP pathologic features. The study shows a higher prevalence of low visual acuity, hyperopia, and astigmatism in the study population compared with the controls. The size of the CTG repeat expansion had an impact on BCVA in all subgroups with lower values in individuals with larger expansion size. In childhood DM1, individuals with high hyperopia and astigmatism had greater CTG repeat expansion size than those without. No true cataract was found. Subtle nonspecific fundus changes were present in addition to VEP pathology. Children and adolescents with DM1 have a variety of visual function pathologies, and DM1 has an impact on the developing visual system, necessitating early ophthalmologic assessment and follow-up.

Cognition and adaptive skills in myotonic dystrophy type 1: a study of 55 individuals with congenital and childhood forms

To investigate cognitive abilities and adaptive skills in children and adolescents with myotonic dystrophy type 1 (DM1) and correlate the findings to the cytosine-thymine-guanine (CTG) repeat expansion size. Cognitive level was assessed in 55 children and adolescents with DM1 (31 males, 24 females; mean age 12y 1mo, SD 5y 1mo; range 2y 7mo-21y 5mo) divided into the following categories: severe congenital DM1 (n=19), mild congenital DM1 (n=18), and childhood DM1 (n=18). The Griffiths Mental Developmental Scale, the Wechsler Scales, and the Vineland Adaptive Behavior Scales (VABS) for adaptive skills were used for this purpose. Learning disability was found in 95% of the severe congenital group, 83% of the mild congenital group, and 89% of the childhood DM1 group. The more severe the form of DM1, the lower the full-scale IQ (FSIQ; r(s)=0.28, p=0.044). The individuals with severe congenital and childhood DM1 had a significantly higher verbal IQ than performance IQ (severe congenital: mean difference 5.7, SD 5.7, p=0.008; childhood DM1: mean difference 9.8, SD 18.0, p=0.038). CTG repeat expansion correlated negatively with FSIQ (r(s)=-0.63, p<0.006). Almost all participants showed poor results on the VABS. There was a positive relationship between cognitive level and adaptive skills in the mild congenital (r(s)=0.95, p<0.01) and childhood DM1 groups (r(s)=0.92, p<0.01). Children and adolescents with DM1 exhibit significant cognitive and adaptive problems.

New Analysis Method of Myotonic Dystrophy 1 Based on Quantitative Fluorescent Polymerase Chain Reaction

Molecular genetic testing of myotonic dystrophy type 1 (DM1) is based on the identification and determination of a cytosine-thymine-guanine (CTG) repeat expansion in the DMPK gene. This is usually done by Southern blot analysis-a time-consuming and very laborious technique requiring high molecular weight DNA. The aim of our study was to develop a highly sensitive, rapid, and cost-effective molecular analysis characterizing the CTG repeat region of the DMPK gene based on a two-step polymerase chain reaction (PCR) protocol. (1) For the detection of alleles of up to 100 repeats, a quantitative fluorescent (QF) amplification with primers flanking the repeat region of the DM1 locus and two reference genes (PAX2 and DHCR7) for standardization was used. By this method it was possible to identify both homozygous and heterozygous DM1 alleles. (2) Long PCR was only performed if a single wild-type allele was detected that gave a QF-PCR signal of only half intensity compared to a homozygous sample. The results obtained using combined QF and Long PCR are highly accurate compared with Southern blot analysis. We conclude that our new rapid analysis is reliable for genetic testing of DM1 patients.

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans

Myotonic dystrophy type 1 (DM1) is an autosomal-dominant muscular dystrophy caused by expansion of cytosine-thymine-guanine (CTG) trinucleotide repeats in the myotonic dystrophy protein kinase (DMPK) gene. The clinical features of DM1 are multisystemic and highly variable, and the unstable nature of CTG expansion causes wide genotypic and phenotypic presentations. The aim of this study was to characterize the molecular and clinical spectra of DM1 in Koreans. The CTG repeats of 283 Korean individuals were tested by PCR fragment analysis and Southern blot. The following characteristics were assessed retrospectively: spectrum of CTG expansions, clinical findings, genotype-phenotype correlation, anticipation, and genetic instability. One-hundred twenty-four patients were confirmed as DM1 by molecular tests, and the CTG expansions ranged from 50 to 2,770 repeats (median 480 repeats). The most frequent clinical features were myotonia, muscular weakness, and family history. Patients with muscular weakness or dysfunction of the central nervous system harbored larger CTG expansions than those without each symptom (P<0.05). The age of onset was inversely correlated with the size of the CTG expansion (gamma=-0.422, P<0.001). The instability of CTG expansion representing as the maximum difference between sibships was observed from 50 to 700 repeats in nine families. Clinical anticipation and the increase in CTG repeat were significantly higher in maternally transmitted alleles (P=0.002). Molecular genetic tests are not only essential for diagnosis, but also helpful for suggesting the spectrum and relationship between genotype and phenotype in Korean DM1 patients.

Ophthalmological findings in childhood onset myotonic dystrophy type 1

Abstract Purpose Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder, characterised by increasing severity and anticipation (progressive expansion of the repeat size and earlier onset in successive generations). It is caused by an expanded cytosine‐thymine‐guanine (CTG) triple repeat expansions in the myotonic protein kinase gene located on chromosome 19. Muscle wasting, myotonia and cataract are features of classical DM1, while congenital and childhood DM1 are also present with CNS involvement and cognitive impairments. The aims of the current study were to describe ophthalmological findings in individuals with childhood onset DM1, to correlate the ophthalmological findings with the size of the CTG expansions, inheritance and the age of onset and presenting clinical symptoms. Methods Sixty‐ two children and adolescents were eligible for the study and 49 accepted to participate. All had clinical symptoms &lt;10 years of age and were diagnosed with &gt;40 CTG repeats &lt;18 years of age. According to the age of onset and presenting clinical symptoms, the subjects were divided into three subgroups: I/ severe congenital II/ mild congenital and III/ childhood DM1. Results High hyperopia, heterotropia, subnormal VA, motility abnormalities and nystagmus were common features of congenital onset DM1. No cataract was found and ptosis was rare while pseudoptosis and motility disorders occurred frequently among individuals with high number of CTG repeats. Conclusion Ophthalmological pathology was common and individuals with severe congenital DM1 were present with the highest frequency. Number of CTG repeats affected the motility and pseudoptosis while inheritance had no influence on ophthalmological abnormalities.

Neuromuscular excitability properties in myotonic dystrophy type 1

Objective To study neuromuscular excitability in patients with dystrophia myotonica type 1 (DM1). Methods The neuromuscular recovery cycle following motor nerve stimulation was assessed in 16 DM1 patients who had no sign of peripheral neuropathy or diabetes. Compound muscle action potentials were recorded from the adductor digiti minimi muscle to ulnar nerve stimulation at the wrist. Paired pulses were delivered, consisting of a conditioning stimulus of supramaximal intensity, followed by a submaximal test stimulus. Interstimuli intervals (ISIs) ranged between 1 and 8 ms. Durations of the absolute and relative refractory periods (ARP, RRP) and percentages of refractoriness and supernormality at ISIs of 2.6 and 7 ms, respectively, were computed using a subtraction method. The results obtained in the series of DM1 patients were compared to those obtained in six patients with other forms of myotonia and to normative values established in a series of age-matched healthy subjects. Correlations were made between excitability parameters, the number of cytosine–thymine–guanine (CTG) repeats, and the severity of myotonia, scored clinically. Results Compared to controls, DM1 patients presented prolonged durations of ARP and RRP, increased refractoriness and reduced supernormality. The decrease in refractoriness correlated with both the number of CTG repeats and the severity of myotonia. Conclusions Changes in the recovery cycle following supramaximal motor nerve stimulation revealed the existence of subtle alterations of neuromuscular excitability in DM1 patients. Significance Increase in refractoriness together with a reduced supernormality was consistent with a process of membrane depolarization. Such a depolarization may be related to the loss of chloride channels or to alterations in sodium conductance in the motor axon or the muscle fiber.

Analysis of the DMPK gene CTG repeat in healthy Brazilians

Myotonic dystrophy (DM) is a neuromuscular disorder caused by the expansion of the cytosine-thymine-guanine (CTG) repeat of the myotonic dystrophy protein kinase gene (DMPK). This repeat is highly polymorphic in healthy individuals [(CTG)5-37], and it has been proposed that expanded CTG alleles originated from larger sized normal alleles [(CTG)19-37]. According to this hypothesis, a positive correlation should be expected between the frequency of these large-sized normal alleles and the prevalence of the disorder in a population. We determined the distribution of CTG alleles of the DMPK gene in 156 healthy Brazilians from Rio de Janeiro city. Our analyses of 312 chromosomes detected 20 different alleles ranging in size from 5 to 27 CTG repeats, with 24 alleles having more than 18 repeats (7.69%). This frequency of (CTG)319 alleles observed in our population suggests that the prevalence of DM in Rio de Janeiro should not be different from the prevalence in European populations.

Decreased expression of DMPK: correlation with CTG repeat expansion and fibre type composition in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a trinucleotide repeat-expansion, cytosine-thymine-guanine (CTG)n, in the 3' untranslated region of a gene encoding the myotonic dystrophy protein kinase (DMPK). To correlate CTG expansion and protein expression, we studied muscle specimens from 16 adult DM1 patients using three anti-DMPK antibodies for immunoblotting. We estimated the amount of the full-length DMPK (85 kDa) in muscle biopsies from normal controls and from DM1 patients carrying different (CTG)n expansions. We found that DMPK concentration was decreased to about 50% in DM patients' muscles; the protein decrease did not seem correlated with the CTG repeat length. However, the fibre type composition in skeletal muscle seemed somehow to affect DMPK decrease, as the lowest level of the enzyme was found in patients with the lowest content of type 1 fibre.

Familial clustering of muscular and cardiac involvement in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is associated with both skeletal and cardiac muscle involvement. The aim of the present study was to determine whether familial clustering is observed in the severity of muscle involvement in DM1. We evaluated 51 sibling groups constituting 112 patients with genetically-verified DM1. The siblings were similar to each other in age, cytosine-thymine-guanine (CTG) repeat length, age at disease onset, muscular impairment rating score, and electrocardiographic markers of cardiac conduction disease. After adjusting for the similarities between siblings in age and CTG repeat length, the siblings remained similar to each other in measures of both skeletal and cardiac muscle involvement. These results suggest that factors other than CTG repeat length play a role in the severity and progression of the degenerative skeletal and cardiac muscle disease in DM1.