DYNC1H1新突变致显性遗传脊髓性肌萎缩症伴轻度认知障碍一家系并文献回顾
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南京医科大学附属儿童医院康复科 南京医科大学附属儿童医院神经内科

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国家自然科学基金青年基金(81401864);江苏省科教强卫青年人才(QNRC2016089);江苏省妇幼保健协会科研项目(FYX201907);南京市卫健委一般性课题(YKK19108)。


Novel DYNC1H1variant causes dominant inherited spinal muscular atrophy with mild cognitive impairment in a family and literature reviewZhu Min1, Song Jianmin2, Lu Fen,Du Senjie1, Zhao Xiaoke1, Tang Jian1
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Tang Jian

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    摘要:

    目的 分析1例罕见常染色体显性遗传脊髓性肌萎缩症-下肢1型(SMALED1)家系的分子遗传学特征。方法 回顾性分析2021年02月在南京市儿童医院康复科确诊的1例幼儿起病常染色体显性遗传脊髓性肌萎缩症1型患儿及其家人的临床表现、实验室检查及基因检测结果。通过文献检索,搜集并总结相关报道案例的基因型-表型关联。结果 患儿,男,2岁龄,表现为轻度全面发育迟缓,以运动功能障碍为主。患儿1岁余出现运动发育落后,表现为双下肢近端肌萎缩、无力,双足外翻,独站不稳,不能独走,辅助行走呈鸭步态。查体膝反射消失;肌电图提示脊髓前角细胞或根性损害,脑影像学无显著异常。患儿母亲及外祖母有相同的运动障碍表现。基因检测鉴定患儿DYNC1H1基因上有新的未报道错义突变c.3326A>G(p.Y1109C),证实其遗传自母亲和外祖母。本例SMALED1突变位点与以往研究吻合,但不能解释精神发育异常表型。结论本研究鉴定了1个新突变,扩展了DYNC1H1致病性变异谱。先证者伴有精神发育异常证实以往研究中的脑皮质发育异常缺少基因型-表型关联,同时表明新变异p.Y1109C所关联表型存在异质性。

    Abstract:

    Objective To analyze the molecular genetic characteristics of a rare case of autosomal dominant spinal muscular atrophy-lower limb type 1 (SMALED1) family. MethodsRetrospective analysis of the clinical manifestations, laboratory examinations and genetic testing ina child and his family members diagnosed with SMALED1in the Rehabilitation Department of Nanjing Children"s Hospital in February, 2021. By literature review, we collect and summarize the genotype-phenotype associations of previously reported cases. Results The proband was a 2-year-old boy with mild global developmental delay, mainly motordevelopmental delay. The patient developed motor disorder after 1 year old, manifested as proximal muscular atrophy and weakness of both lower extremities, valgus feet, unstable standing alone, unable to walk alone, and duck gait in assisted walking. Physical examination showed his knee reflex disappeared; the electromyography showed spinal cord anterior horn,or root, cells lesions, and there was no significant abnormality in brain imaging. His mother and grandmother of the child had the same dyskinesia. Genetic tests identified a novelmissense mutation c.3326A>G (p.Y1109C) in the DYNC1H1 gene inthe affectedmemebers, andit was confirmedbeinginherited from his mother and grandmother. The site of SMALED1-associated in this study is consistent with previous studies, but it cannot explain the phenotype of mental development. Conclusion This study identified a novel mutation, which expanded the DYNC1H1 pathogenic variant spectrum. The proband with mental impairments confirms the lack of genotype-phenotype association of cortical dysplasias in previous studies, and it also shows that the phenotype associated with the novel variant p.Y1109C may be heterogeneous.

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  • 收稿日期:2021-10-22
  • 最后修改日期:2023-03-25
  • 录用日期:2023-07-09
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