• 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.

• Annals of Clinical Neurophysiology
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• 제6권1호
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• pp.61-63
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• 2004

The copy numbers of the CTG repeats are known to relate to the severity of clinical symptoms for myotonic dystrophy. The positive correlation between clinical manifestations and CTG repeat size has been demonstrated previously. A genetically confirmed myotonic dystrophy patient with 90 CTG repeat number had more severe clinical manifestation than brother with 120 CTG repeats, in adulthood.

• 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.

• 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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• 제1권1호
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• pp.23-26
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• 1997

Myotonic dystrophy (DM) is caused by the expansion of CTG trinucleotide repeat near the 3' end of the gene encoding for a member of protein kinase gene family (DMPK). The normal range of the CTG repeat was determined in 178 normal individuals (141 unrelated individuals and 37 of 9 families) by polymerase chain reaction (PCR), polyacrylamide gel electrophoresis and silver staining method. And the expansion of the CTG repeats in a DM family was analyzed with Southern analysis. In normal population, the range of CTG repeat is between 5 and 34 and 19 different alleles were observed in that range, and $(CTG)_{11-14}$ alleles were predominant. 4 members of an affected family showed the 0.5-2.0 kb size expansion of CTG repeats. In this study we could predict the incidence of DM in Korea as 1 in 20,000 and we could establish the diagnostic procedure for myotonic dystrophy.

• 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.

• Clinical and Experimental Pediatrics
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• 제50권9호
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• pp.868-874
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• 2007

목 적 : 선천성 근육긴장성 이영양증(congenital myotonic dystrophy, CDM) 환자의 주산기 병력, 영아기 및 소아기의 증상, 그리고 환자 어머니의 임상양상을 확인하여, 임상진단에 도움이 될 수 있는 특징적인 소견과, DMPK유전자의 CTG 서열반복 수와 운동발달 관계를 확인하고자 하였다. 방 법 : 2001년 1월부터 2006년 9월까지 삼성서울병원에서 DMPK 유전자 검사를 통해 CDM으로 확진된 환자 8명(남자 2명, 여자 8명)을 대상으로 의무기록과 DMPK 유전자 검사를 후향적으로 분석하였다. 결 과 : 진단 시 환자들의 연령은 7일에서 45개월(중앙값: 20.5 개월)이었으며, 환자들은 발달지연, 수유곤란, 그리고 근육긴장저하를 주소로 내원하였다. 3명의 환자에서 산전 초음파 상 원인 불명의 양수과다증이 확인되었다. 모든 환자에서 운동발달지연이 있었으며, 연령이 증가할수록 호전되었다. 모든 환자들의 어머니에서 전형적인 근병증의 모습과 근육긴장증을 확인하였고, 4명의 환자에서는 어머니 형제의 가족력을 확인하였다. DMPK유전자의 CTG 서열반복 수는 1,000-2,083(중앙값: 1,533.5)의 분포를 보였으며, 운동발달 중 혼자 걷기의 지연 정도와 유의한 상관관계는 없었다. 1명의 환자에서 세대간 예견효과를 확인하였다. 결 론 : CDM 환자는 산전초음파에서 양수과다증, 내반첨족, 태동의 저하 등의 소견을 보이고, 출생 후 근육긴장저하와 연관된 호흡곤란, 수유곤란, 그리고 발달지연 등의 증상을 나타낸다. 모든 환자들의 어머니는 특징적인 근병증의 외양과 근육긴장증을 가지고 있어, 산모에 대해 이러한 소견을 확인하는 것이 산전진단에 중요한 단서가 된다. CDM에서 근육긴장저하와 연관된 증상은 연령이 증가할수록 호전되며, DMPK 유전자의 CTG 서열반복 수와 운동발달 중 혼자 걷기 시기 간의 유의한 연관은 없었다.

• 대한소아신경학회지
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• 제26권4호
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• pp.189-196
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• 2018

목적: 늘어지는 영아 증후군은 중추신경계 이상, 말초 신경계 이상 혹은 둘 모두의 이상으로 발생할 수 있다. 늘어지는 영아에서 원인을 진단하는 것은 환아의 치료와 발달 예후를 결정하는 중요한 요소로 현재까지 다양한 진단 알고리듬이 제안되고 있다. 본 논문에서는 늘어지는 영아 증후군의 원인에 대한 새로운 분류 및 증상 발현 시기에 따른 원인, 그리고 이들의 발달 예후에 대해 연구하였다. 방법: 2005년부터 2016년까지 세브란스병원에 내원한 늘어지는 영아들을 대상으로 EMR 차트를 후향적으로 분석하여 진단 및 임상적 특징을 분석하였고 환아들의 발달에 대해 보호자에게 일대일 전화인터뷰를 통해 조사하였다. 결과: 전체 116명의 환아 중에 원인에 대한 확진을 받은 경우가 69명으로 전체 진단율이 59.5%이었고 이들 중 Prader-Willi syndrome, myotonic dystrophy, spinal muscular atrophy가 가장 흔한 진단이었다. 전 연령대에 걸쳐 Prader-willi syndrome이 가장 흔한 진단이었고 특히 1개월 미만 증상 발현군에서는 Prader-willi syndrome, myotonic dystrophy, early infantile epileptic encephalopathy가 흔한 3가지의 진단이었다. 발달 예후 면에서 원인군 중 combined hypotonia에서 전 영역에 걸쳐 가장 나쁜 예후를 보였다. 결론: 현재까지의 논문과 본 논문에서의 늘어지는 영아 증후군에 대한 진단율은 유사했고 각 연령에 따른 흔한 진단에 대해서도 알아보았다. 발달 예후가 가장 나쁜 combined hypotonia군에 속하는 진단으로 확진되거나 의심되는 경우 초기 진단시부터 발달에 대해 체계적이고 단계적인 추적관찰이 필요하다.