该文报道1例常染色体隐性痉挛性截瘫55型患儿的临床特征及C12orf65基因突变特点。患儿女，8岁，5岁起病，以视神经萎缩为主要临床表现，伴有蹲起缓慢和轻度鸭形步态。提取患儿及其父母和哥哥外周血DNA标本，对患儿进行全外显子组和线粒体基因组测序，并进行Sanger测序验证。结果显示患儿C12orf65基因存在c.394C > T和c.447_449delGGAinsGT的复合杂合突变，前者来自父亲，为已知致病突变；后者来自母亲，是一个未见文献报道的新突变。该研究扩展了C12orf65基因突变谱，为患儿病因诊断及该家系的遗传咨询提供了分子依据。
Abstract
This article reports the clinical features and C12orf65 gene mutations of a girl with autosomal recessive spastic paraplegia-55. The 8-year-old girl experienced disease onset at the age of 5 years and had optic atrophy as the main clinical manifestation, with slow movements in standing up and a slight duck-shaped gait. Peripheral blood DNA samples were collected from this child and her parents and brother to perform high-throughput whole-exome sequencing and high-throughput mitochondrial genome sequencing. Sanger sequencing was performed for verification. The results showed two compound heterozygous mutations, c.394C > T and c.447_449delGGAinsGT, in the C12orf65 gene. The former mutation came from her father and was a known pathogenic mutation, and the latter came from her mother and was a novel mutation which had not been reported in literature. This study expands the mutation spectrum of the C12orf65 gene and thus provides a molecular basis for the etiological diagnosis of the child and the genetic counseling of the family.
关键词
常染色体隐性痉挛性截瘫55型 /
C12orf65基因 /
视神经萎缩 /
儿童
Key words
Autosomal recessive spastic paraplegia-55 /
C12orf65 gene /
Optic atrophy /
Child
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参考文献
[1] Antonicka H, Ostergaard E, Sasarman F, et al. Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect[J]. Am J Hum Genet, 2010, 87(1):115-122.
[2] Shimazaki H, Takiyama Y, Ishiura H, et al. A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55)[J]. J Med Genet, 2012, 49(12):777-784.
[3] Heidary G, Calderwood L, Cox GF, et al. Optic atrophy and a Leigh-like syndrome due to mutations in the C12orf65 gene:report of a novel mutation and review of the literature[J]. J Neuroophthalmol, 2014, 34(1):39-43.
[4] Fang XJ, Zhang W, Lyu H, et al. Compound heterozygote mutation of C12orf65 causes distal motor neuropathy and optic atrophy[J]. Chin Med J (Engl), 2017, 130(2):242-244.
[5] Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants:a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5):405-424.
[6] Spiegel R, Mandel H, Saada A, et al. Delineation of C12orf65-related phenotypes:a genotype-phenotype relationship[J]. Eur J Hum Genet, 2014, 22(8):1019-1025.
[7] Pyle A, Ramesh V, Bartsakoulia M, et al. Behr's syndrome is typically associated with disturbed mitochondrial translation and mutations in the C12orf65 gene[J]. J Neuromuscul Dis, 2014, 1(1):55-63.
[8] Imagawa E, Fattal-Valevski A, Eyal O, et al. Homozygous p.V116* mutation in C12orf65 results in Leigh syndrome[J]. J Neurol Neurosurg Psychiatry, 2016, 87(2):212-216.
[9] Buchert R, Uebe S, Radwan F, et al. Mutations in the mitochondrial gene C12orf65 lead to syndromic autosomal recessive intellectual disability and show genotype phenotype correlation[J]. Eur J Med Genet, 2013, 56(11):599-602.
[10] Nishihara H, Omoto M, Takao M, et al. Autopsy case of the C12orf65 mutation in a patient with signs of mitochondrial dysfunction[J]. Neurol Genet, 2017, 3(4):e171.
[11] Wesolowska M, Gorman GS, Alston CL, et al. Adult onset Leigh syndrome in the intensive care setting:a novel presentation of a C12orf65 related mitochondrial disease[J]. J Neuromuscul Dis, 2015, 2(4):409-419.
[12] Tucci A, Liu YT, Preza E, et al. Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy[J]. J Neurol Neurosurg Psychiatry, 2014, 85(5):486-492.
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