[Autosomal dominant spastic paraplegias].
[Autosomal dominant spastic paraplegias].
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DOI：
10.17116/jnevro202112105175
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发表时间：
2021-01-01
影响因子：
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通讯作者：
Ryzhkova, O P
中科院分区：
文献类型：
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作者：
Rudenskaya, G E;Kadnikova, V A;Ryzhkova, O P
目的：估计罕见常染色体显性痉挛性截瘫在一组dna确诊家庭中的比例和频谱，并探讨其分子和临床特征。材料与方法：采用临床、家谱、分子遗传学（大规模平行测序、痉挛性截瘫面板、全外显子组测序、多重连接依赖性扩增、Sanger测序）和生物信息学方法研究了10个AD-SPG家族：SPG6 （n=1）、SPG8 （n=2）、SPG9A （n=1）、SPG12 （n=1）、SPG17 （n=3）、SPG31 （n=2）。结果与结论：在6个基因中检测到9个杂合突变，包括NIPA1中常见的新突变p.Gly106Arg (SPG6)，孤立病例中早期报道的突变p.Val626Phe (SPG8)， 4例患者中WASHC5 （SPG8）中新的p.Val695Ala， 2例患者中RTN2 （SPG12）中新的突变p.Thr301Arg。在一个有4名患者的家庭中发现了REEP1 （SPG31）的新突变c.105+4A>G，在一个有3名患者的家庭中发现了REEP1 （SPG31）的早前突变p.Lys101Lys，在两个同卵双胞胎中发现了ALDH18A1 （SPG9A）的新突变p.Arg252Gln；3例BSCL2患者（SPG17）中常见的p.Ser90Leu突变和2例BSCL2患者（SPG17）中罕见的p.l e363pro突变。SPG6、SPG8、SPG12和SPG31表现为“纯”表型，其中SPG31的良性病程最多。SPG31家族发病年龄不同，而SPG6家族发病年龄不典型。SPG9A和SPG17患者出现“复杂”截瘫；2个家庭的一名儿童和一名青少年没有SPG17典型的手部肌萎缩症，但可能在以后发展。
OBJECTIVE: To estimate the proportion and spectrum of infrequent autosomal dominant spastic paraplegias in a group of families with DNA-confirmed diagnosis and to investigate their molecular and clinical characteristics.MATERIAL AND METHODS: Ten families with 6 AD-SPG: SPG6 (n=1), SPG8 (n=2), SPG9A (n=1), SPG12 (n=1), SPG17 (n=3), SPG31 (n=2) were studied using clinical, genealogical, molecular-genetic (massive parallel sequencing, spastic paraplegia panel, whole-exome sequencing, multiplex ligation-dependent amplification, Sanger sequencing) and bioinformatic methods.RESULTS AND CONCLUSION: Nine heterozygous mutations were detected in 6 genes, including the common de novo mutation p.Gly106Arg in NIPA1 (SPG6), the earlier reported mutation p.Val626Phe in WASHC5 (SPG8) in isolated case and the novel p.Val695Ala in WASHC5 (SPG8) in a family with 4 patients, the novel mutation p.Thr301Arg in RTN2 (SPG12) in a family with 2 patients, the novel mutation c.105+4A>G in REEP1 (SPG31) in a family with 4 patients and the reported earlier p.Lys101Lys in REEP1 (SPG31) in a family with 3 patients, the known de novo mutation p.Arg252Gln in ALDH18A1 (SPG9A) in two monozygous twins; the common mutation p.Ser90Leu in BSCL2 (SPG17) in a family with 3 patients and in isolated case, reported mutation p.Leu363Pro in a family with 2 patients. SPG6, SPG8, SPG12 and SPG31 presented 'pure' phenotypes, SPG31 had most benign course. Age of onset varied in SPG31 family and was atypically early in SPG6 case. Patients with SPG9A and SPG17 had 'complicated' paraplegias; amyotrophy of hands typical for SPG17 was absent in a child and in an adolescent from 2 families, but may develop later.