• Journal of Interdisciplinary Genomics
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• 제3권2호
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• pp.25-29
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• 2021

Myotonic muscular dystrophy is a disease characterized by progressive muscle weakness with myotonia and multiorgan involvement. Two subtypes have been recognized; each subtype is caused by nucleotide repeat expansion. So far, there has been no cure for myotonic muscular dystrophy. In this article, we introduce ongoing clinical trials for new drugs to modify disease course by correcting genetic derangement or its downstream in myotonic dystrophy type 1.

• Annals of Clinical Neurophysiology
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• 제13권1호
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• pp.48-50
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• 2011

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disorder caused by the expansion of cytosine-thymine-guanine (CTG) repeats in the myotonic dystrophy protein kinase (DMPK) gene. Some literatures indicated that DM1 had incidental CNS lesions such as white matter lesions and diffuse gray matter atrophy. We report a patient with DM1 whose brain magnetic resonance image (MRI) showed multifocal hyperintense lesions and cystic lesion on both frontotemporoparietal lobes.

• Genomics & Informatics
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• 제7권4호
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• pp.181-186
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• 2009

Myotonic dystrophy type 1 (DM1), which is a dominantly inherited neurodegenerative disorder, results from a CTG trinucleotide repeat expansion in the 3'-untranslated region (3'-UTR) of the myotonic dystrophy protein kinase (DMPK) gene. Retention of mutant DMPK (mDMPK) transcripts in the nuclei of affected cells has been known to be the main cause of pathogenesis of the disease. Thus, reducing the RNA toxicity through elimination of the mutant RNA has been suggested as one therapeutic strategy against DM1. In this study, we suggested RNA replacement with a trans -splicing ribozyme as an alternate genetic therapeutic approach for amelioration of DM1. To this end, we identified the regions of mDMPK 3'-UTR RNA that were accessible to ribozymes by using an RNA mapping strategy based on a trans-splicing ribozyme library. We found that particularly accessible sites were present not only upstream but also downstream of the expanded repeat sequence. Repair or replacement of the mDMPK transcript with the specific ribozyme will be useful for DM1 treatment through reduction of toxic mutant transcripts and simultaneously restore wild-type DMPK or release nucleus-entrapped mDMPK transcripts to the cytoplasm.

• Journal of Genetic Medicine
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• 제13권2호
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• pp.105-110
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• 2016

Congenital myotonic dystrophy (CMD) which is transmitted in an autosomal-dominant manner, can also be observed in newborns born to asymptomatic parents who have a myotonic dystrophy type 1 or premutation allele, especially from the mother. A mother with myotonic dystrophy could be subfertile and the pregnancy could be complicated with the risk of a preterm birth. Newborns with CMD may demonstrate symptoms such as hypotonia and poor motor activity, as well as respiratory and feeding difficulties. Additionally, CMD has a high mortality rate at birth. Detection of the signs and symptoms during pregnancy is helpful for a prenatal diagnosis of CMD in cases where the family history is not known.

• 대한근전도전기진단의학회지
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• 제20권2호
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• pp.148-152
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• 2018

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disorder and one of the most common muscular dystrophies affecting adults. Charcot-Marie-Tooth (CMT) disease, a common hereditary neuropathy, is characterized by atrophy of the distal limbs and peripheral nerve abnormalities. The authors report a rare case involving a 24-year-old female who was diagnosed simultaneously with both DM1 and CMT1A based on the results of a nerve conduction study (NCS). The patient, who had previously been diagnosed with DM1, was admitted for lower extremity pain. Her electrodiagnostic examination continued to reveal severe sensorimotor demyelinating polyneuropathy, and a genetic study was performed to confirm whether she had other hereditary neuropathies, except DM1, that suggested CMT1A, the most common phenotype of CMT. Severe abnormalities in an NCS in a DM1 patient may suggest the incidental coexistence of hereditary neuropathies, and further evaluations, such as genetic studies, should be performed for proper diagnosis.

• Clinical and Experimental Pediatrics
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• 제62권2호
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• pp.55-61
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• 2019

Purpose: Myotonic 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. Methods: We 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. ${\geq}1,000$). Results: We 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. Conclusion: Clinical 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.

• The Korean Journal of Physiology and Pharmacology
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• 제9권1호
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• pp.1-8
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• 2005

Myotonic Dystrophies type 1 and 2 (DM1/2) are neuromuscular disorders which belong to a group of genetic diseases caused by unstable CTG triplet repeat (DM1) and CCTG tetranucleotide repeat (DM2) expansions. In DM1, CTG repeats are located within the 3' untranslated region of myotonin protein kinase (DMPK) gene on chromosome 19q. DM2 is caused by expansion of CCTG repeats located in the first intron of a gene coding for zinc finger factor 9 on chromosome 3q. The CTG and CCTG expansions are located in untranslated regions and are expressed as pre-mRNAs in nuclei (DM1 and DM2) and as mRNA in cytoplasm (DM1). Investigations of molecular alterations in DM1 discovered a new molecular mechanism responsible for this disease. Expansion of un-translated CUG repeats in the mutant DMPK mRNA disrupts biological functions of two CUG-binding proteins, CUGBP and MNBL. These proteins regulate translation and splicing of mRNAs coding for proteins which play a key role in skeletal muscle function. Expansion of CUG repeats alters these two stages of RNA metabolism in DM1 by titrating CUGBP1 and MNBL into mutant DMPK mRNA-protein complexes. Mouse models, in which levels of CUGBP1 and MNBL were modulated to mimic DM1, showed several symptoms of DM1 disease including muscular dystrophy, cataracts and myotonia. Mis-regulated levels of CUGBP1 in newborn mice cause a delay of muscle development mimicking muscle symptoms of congenital form of DM1 disease. Since expansion of CCTG repeats in DM2 is also located in untranslated region, it is predicted that DM2 mechanisms might be similar to those observed in DM1. However, differences in clinical phenotypes of DM1 and DM2 suggest some specific features in molecular pathways in both diseases. Recent publications suggest that number of pathways affected by RNA CUG and CCUG repeats could be larger than initially thought. Detailed studies of these pathways will help in developing therapy for patients affected with DM1 and DM2.

• Clinical and Experimental Pediatrics
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• 제49권11호
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• pp.1158-1166
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• 2006

목 적 : 늘어지는 증상을 주소로 신생아 및 소아 중환자실에 입원한 영아들의 임상적, 신경학적, 전기생리학적 소견 및 유전적 진단 결과를 통한 분석을 통해 늘어지는 영아 증후군의 진단적 분류 및 진단 방법에 대한 고찰을 하고자 하였다. 방 법 : 1993년도부터 2005년까지 13년간 서울대학교 병원 어린이병원 신생아 중환자실 및 소아 중환자실에 늘어지는 증상을 주된 주소로 입원한 영아들을 대상으로 하였다. 후향적 의무기록조사를 통해 임상 소견 및 검사 소견들을 조사하였고 최종 진단명을 분류하였다. 결 과 : 늘어지는 증상을 주소로 내원한 영아들은 21명이었다. 최종 진단명은 중추성 기원이 7명(33.3%), 말초성 기원이 11명(52.4%), 나머지 3명은(14.3%) 두 그룹 중 어느 그룹으로도 분류되지 못하였다. 중추성 기원은 저산소-허혈성 뇌증이 3명으로 가장 많았고, 그 외에 Prader-Willi 증후군 2명, 염색체 이상 1명, 일과성 저긴장증 1명이 있었다. 말초성 기원은 myotubular 근병증이 4명으로 가장 많았고, SMA 1형이 3명, 선천성 근긴장성 이영양증 2명, 선천성 근이영양증 1명, 그 외 분류되지 않은 운동신경질환 1명이 있었다. 가족력이 있었던 경우는 말초성 그룹에서만 3명이 있었고, 신경학적 검진 상 근력은 중추성 그룹에서 평균 Grade 3 이상이었고 건반사도 활발하게 나타난 경우가 많아 다른 그룹의 환자들과 차이를 보였다. 검사상의 소견은 근전도 검사에서 말초성 그룹이 66%의 민감도를 보였고 근생검은 말초성 그룹에서 진단적이었다. 중추성 그룹에서 뇌 영상 검사가 진단적이었고 진단율이 높지는 않았지만 Prader-Willi FISH 나 염색체 검사를 통해 진단이 되었던 경우가 있었다. 그외의 분자 유전학적 검사로 확진 가능한 말초성 그룹의 환자들이 있었다. 입원 기간 및 기관 삽관 기간은 말초성 그룹에서 현저하게 길었고, 추적 관찰 시 사망 및 심한 발달 지체의 비율도 말초성 그룹에서 높게 나타났다. 결 론 : 본 연구의 늘어지는 영아들의 임상상을 바탕으로 진단적 분류를 시행하고 각 진단 분류에 유용한 검사를 순서대로 진행시킨다면 효과적인 진단이 이루어질 수 있을 것이다.