外显子组测序提示常染色体显性下尿路功能障碍和轻度遗传性痉挛性截瘫中DSTYK的一种新的杂合错义变异。

IF 2.4 Q1 PEDIATRICS
Clara Vidic, Marcin Zaniew, Szymon Jurga, Holger Thiele, Heiko Reutter, Alina C Hilger
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引用次数: 1

摘要

DSTYK编码双丝氨酸/苏氨酸和酪氨酸蛋白激酶。DSTYK与常染色体显性先天性肾脏和尿路异常以及常染色体隐性遗传性痉挛性截瘫23型有关。在这里,我们报告了一位父亲和他的两个异卵双胞胎儿子,他们携带一种新的DSTYK杂合错义变异,由于排尿功能障碍而出现早发性下尿路功能障碍。此外,在疾病的后期,两个儿子都表现为双侧下肢痉挛,反射快,失神发作。材料和方法:对患病父亲及其患病儿子进行外显子组测序。儿子临床表现为排尿犹豫,排尿功能障碍,夜间尿失禁,直到青春期,而父亲报告排尿困难。在男孩中,膀胱镜检查排除了尿道瓣膜,发现膀胱颈肥大和膀胱小梁。此外,两个儿子都在儿童早期被诊断为缺乏性癫痫。外显子组数据的过滤主要集中在罕见的(MAF < 0.01%),常染色体显性变异,预测是有害的,位于外显子组的高度保守区域。结果:外显子组分析鉴定出一种新的杂合错义变异(c.271C> a (p.Leu91Met))在DSTYK中与疾病分离。计算机预测分析一致认为该变异是有害的,表明该变异在家族中是致病的。结论:据我们所知,这是首次报道与DSTYK中一种新的杂合显性错义变异相关的早发性排尿功能障碍、癫痫发作和双侧下肢痉挛。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Exome sequencing implicates a novel heterozygous missense variant in DSTYK in autosomal dominant lower urinary tract dysfunction and mild hereditary spastic paraparesis.

Exome sequencing implicates a novel heterozygous missense variant in DSTYK in autosomal dominant lower urinary tract dysfunction and mild hereditary spastic paraparesis.

Introduction: DSTYK encodes dual serine/threonine and tyrosine protein kinase. DSTYK has been associated with autosomal-dominant congenital anomalies of the kidney and urinary tract and with autosomal-recessive hereditary spastic paraplegia type 23. Here, we report a father and his two dizygotic twin sons carrying a novel heterozygous missense variant in DSTYK, presenting with early onset lower urinary tract dysfunction due to dysfunctional voiding. Moreover, in the later course of the disease, both sons presented with bilateral spasticity in their lower limbs, brisk reflexes, and absence seizures.

Materials and methods: Exome sequencing in the affected father and his affected sons was performed. The sons presented clinically with urinary hesitancy, dysfunctional voiding, and night incontinence till adolescence, while the father reported difficulty in voiding. In the sons, cystoscopy excluded urethral valves and revealed hypertrophy of the bladder neck and trabeculated bladder. Additionally, both sons were diagnosed with absence epilepsy in early childhood. Filtering of exome data focused on rare (MAF < 0.01%), autosomal-dominant variants, predicted to be deleterious, residing in highly conserved regions of the exome.

Results: Exome analysis identified a novel, heterozygous missense variant (c.271C>A (p.Leu91Met)) in DSTYK segregating with the disease. In silico prediction analyses uniformly rated the variant to be deleterious suggesting the variant to be disease-causing in the family.

Conclusion: To the best of our knowledge, this is the first report of early onset dysfunctional voiding, seizures, and bilateral spasticity of the lower limbs associated with a novel heterozygous dominant missense variant in DSTYK.

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