Brain : The neurology team at Huashan Hospital found that far-end myopathy is the most common disease-caused mutation in China

Progressive muscular dystrophy is a group of hereditary skeletal muscular dystrophy disease, pathologically with skeletal fibrosis, necrosis as the main characteristics, clinically with slow development of muscle atrophy, muscle weakness as the main performance, some types can also be tired of the heart, bone system.
has traditionally been divided into seven subtypes of large-scale muscular dystrophy, Emery-Dreifuss muscular dystrophy, shoulder-to-shoulder muscular dystrophy, ophthalmary muscular dystrophy, eye-type muscular dystrophy, far-end muscular dystrophy and congenital muscular dystrophy.
Among them, ophthalmology far-end myopathy (OPDM) is a kind of rare hereditary myopathy that mainly affects the outer eye muscle, throat muscle, face muscle and limb far-end muscle group, first described by Japanese scholars in 1977, but the disease's pathogenic gene has not been found for many years.
with the rise of three generations of sequencing technology, in early 2019, Japanese scholars first discovered the presence of LRP12 gene 5'UTR region CGG repeated amplification, called OPDM1, in the OPDM queue in Japan.
Recently, the research team of neuromyopathy in neurology department of Huashan Hospital affiliated with Fudan University, in cooperation with the National Key Laboratory of Genetic Engineering of Fudan University School of Life Sciences, found that the recurrence abnormal amplification of GIPC1 gene 5' non-translation zone (5'UTR) CGG was negatively related to the disease's high chain, and the number of repeat amplifications was negatively corresed with the age of onset.
the results were published in brain, an international authoritative journal of neurology.
the study teamed up with several units of the Pan-Long River Delta Myopathy Alliance, including Zhongshan Hospital affiliated with Fudan University, Tongren Hospital affiliated with Shanghai Jiaotong University, Tongji Hospital affiliated with Tongji University in Shanghai, and Wuhan First Hospital.
team followed an OPDM family for 11 years and confirmed that the GIPC1 gene 5'UTR region CGG was repeatedly amplified to the OPDM and consistent pathogenic gene, called OPDM2.
12 members of the family linee became ill in 7 generations.
genetic methods such as second-generation sequencing, thromosome analysis and chain analysis were used to locate the disease chain area to a section with chromosome 19 with a length of 4.5MB.
three generations of sequencing, it was found that there was cGG repeated abnormal amplification in the GIPC1 gene 5'UTR region of the patient.
the presence of abnormal amplification and clinical ideo-esothype co-separation was further determined in the home system by the three-quote PCR and rich GC-PCR methods.
this confirms the pathogenicity of OPDM2 to OPDM.
the study found that disease-caused mutations in the OPDM queue in China were most common with OPDM2 (i.e., repeated amplification of the GIPC1 gene trinucleotides), accounting for about 51.9%, with 70-138 abnormal amplifications.
and only 3.7% of patients were LRP12 gene trinucleotide re-amplification (OPDM1).
addition, the results also found that the GIPC1 gene 5' UTR region CGG repeated amplification in different tissues such as muscle and exodyscies is relatively stable.
But in the process of transmission to children, the number of repetitions can be increased or decreased (≥10 times), and the number of CGG repetition abnormal amplifications is negatively related to the patient's age of onset, further suggesting the pathogenicity of the mutation.
, the results of the study through the latest genetic methods to determine opDM disease-caused genes, foreshadowing china's disease research with major scientific progress.
The first authors of this paper are Dr. Yan Jianying, Department of Neurology, Huashan Hospital affiliated with Fudan University, Wang Weilu, National Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, and Dr. Yue Dongxuan, Department of Neurology, Jing'an District Central Hospital, Shanghai;
: Xi J, et al. 5' UTR CGG repeat expansion in GIPC1 is associated with oculopharyngodistal myopathy. Brain. 2020 Dec 29:awaa426. doi:10.1093/brain/awaa426. MedSci Original Source: MedSci Original Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Original" are owned by Mets Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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