Exome sequencing shows a novel de novo mutation in ATL1
Exome sequencing shows a novel de novo mutation in ATL1
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DOI：
10.1111/ncn3.72
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发表时间：
2014-01-01
影响因子：
0.4
通讯作者：
Takiyama, Yoshihisa
中科院分区：
文献类型：
--
作者：
Koh, Kishin;Ishiura, Hiroyuki;Takiyama, Yoshihisa
背景和目的：我们经历了治疗一名健康父母所生的男性患者，该患者从童年起就出现痉挛性步态，他的儿子和女儿也同样出现痉挛性步态，这增加了患者发生从头突变的可能性。在假设患者基因发生了新突变的前提下，我们对患者及其父母进行了外显子组测序，以确定患者致病突变的基因。结果：共检测到3个新突变，即PLB 1 c.3601T>A p.C1201S，PHF 2 c.2678C>T p.S893L和ATL 1 c.1259A>C p.Q420P。其中两个突变（ATL 1和PHF 2）与该家族的疾病表型共分离。由于该家族中受影响个体的临床表现是典型的痉挛性截瘫3A型，因此新突变结论：ATL 1中的P.Q420P可能是该家系早发性痉挛性截瘫的病因。在本研究中，我们证实了父母-子女三人组的外显子组测序对于建立神经系统疾病患者的分子诊断的有效性和有用性，怀疑有新突变的患者。
Background and Aim: We experienced treating a male patient born to healthy parents, who presented with spastic gait from childhood, and his son and daughter similarly presented with spastic gait, raising the possibility of a de novo mutation in the patient. With the hypothesis of a de novo mutation in the patient, we carried out exome sequencing of the patient and his parents to identify the gene with a disease-causative mutation in the patient.Methods: The genomic DNA obtained from the patient and his parents were subjected to exome sequencing. We applied various filters to identify candidate de novo mutations.Results: We identified three de novo mutations, namely, PLB1 c.3601T>A p.C1201S, PHF2 c.2678C>T p.S893L and ATL1 c.1259A>C p.Q420P. Two of these mutations (ATL1 and PHF2) cosegregated with the disease phenotype in this family. Because the clinical presentations of the affected individuals in this family are typical for spastic paraplegia type 3A, the novel mutation (p.Q420P) in ATL1 is likely the cause of early-onset spastic paraplegia in this family.Conclusion: In the present, study we confirm the efficacy and usefulness of exome sequencing of parent-child trios for establishing the molecular diagnosis of patients with neurological diseases, in whom de novo mutations are suspected.