Rudenskaya G E, Kadnikova V A, Bessonova L A, Sparber P A, Kurbatov S A, Mironovich O L, Konovalov F A, Ryzhkova O P
Bochkov Research Center for Medical Genetics, Moscow, Russia.
Voronezh Regional Clinical Consultative and Diagnostic Center, Vodonezh, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2021;121(5):75-87. doi: 10.17116/jnevro202112105175.
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.
Ten families with 6 AD-SPG: SPG6 (=1), SPG8 (=2), SPG9A (=1), SPG12 (=1), SPG17 (=3), SPG31 (=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.
Nine heterozygous mutations were detected in 6 genes, including the common mutation p.Gly106Arg in (SPG6), the earlier reported mutation p.Val626Phe in WASHC5 (SPG8) in isolated case and the novel p.Val695Ala in (SPG8) in a family with 4 patients, the novel mutation p.Thr301Arg in (SPG12) in a family with 2 patients, the novel mutation c.105+4A>G in (SPG31) in a family with 4 patients and the reported earlier p.Lys101Lys in (SPG31) in a family with 3 patients, the known mutation p.Arg252Gln in (SPG9A) in two monozygous twins; the common mutation p.Ser90Leu in (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.
评估一组经DNA确诊的家族中罕见常染色体显性遗传性痉挛性截瘫的比例和谱系，并研究其分子和临床特征。
采用临床、系谱、分子遗传学（大规模平行测序、痉挛性截瘫检测板、全外显子测序、多重连接依赖探针扩增、桑格测序）和生物信息学方法，对10个家族中的6例常染色体显性遗传性痉挛性截瘫（AD-SPG）进行研究，其中包括SPG6（=1例）、SPG8（=2例）、SPG9A（=1例）、SPG12（=1例）、SPG17（=3例）、SPG31（=2例）。
在6个基因中检测到9个杂合突变，包括SPG6中常见的p.Gly106Arg突变；在1例孤立病例中，早有报道的WASHC5（SPG8）中的p.Val626Phe突变；在一个有4例患者的家族中，SPG8出现新的p.Val695Ala突变；在一个有2例患者的家族中，SPG12出现新的p.Thr301Arg突变；在一个有4例患者的家族中，SPG31出现新的c.105+4A>G突变，在一个有3例患者的家族中，SPG31出现早有报道的p.Lys101Lys突变；在一对单卵双胞胎中，SPG9A出现已知的p.Arg252Gln突变；在一个有3例患者的家族和1例孤立病例中，SPG17出现常见的p.Ser90Leu突变，在一个有2例患者的家族中，SPG17出现早有报道的p.Leu363Pro突变。SPG6、SPG8、SPG12和SPG31表现为“单纯”表型，SPG31病程最为良性。SPG31家族的发病年龄各不相同，SPG6病例的发病年龄异常早。SPG9A和SPG17患者表现为“复杂”截瘫；2个家族中的1名儿童和1名青少年没有SPG17典型的手部肌萎缩，但可能在以后出现。
