Exome sequencing shows a novel de novo mutation in ATL1. Issue 1 (January 2014)

• Record Type: Journal Article
• Authors: Koh, Kishin; Ishiura, Hiroyuki; Miwa, Michiaki; Doi, Koichiro; Yoshimura, Jun; Mitsui, Jun; Goto, Jun; Morishita, Shinichi; Tsuji, Shoji; Takiyama, Yoshihisa
• Is Part Of: Neurology and clinical neuroscience. Volume 2:Issue 1(2014:Jan.)
• Page Start: 1
• Page End: 4
• Publication Date: 2014-01
• Subjects: Neurology -- Periodicals; Neurosciences -- Periodicals; 616.8
• DOI: 10.1111/ncn3.72
• Languages: English
• ISSNs: 2049-4173

Abstract

<abstract abstract-type="main" id="ncn372-abs-0001"> <title>Abstract</title> <sec id="ncn372-sec-0001" sec-type="section"> <title>Background and Aim</title> <p>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 <italic>de novo</italic> mutation in the patient. With the hypothesis of a <italic>de novo</italic> 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.</p> </sec> <sec id="ncn372-sec-0002" sec-type="section"> <title>Methods</title> <p>The genomic DNA obtained from the patient and his parents were subjected to exome sequencing. We applied various filters to identify candidate <italic>de novo</italic> mutations.</p> </sec> <sec id="ncn372-sec-0003" sec-type="section"> <title>Results</title> <p>We identified three <italic>de novo</italic> mutations, namely, <italic>PLB1</italic> c.3601T>A p.C1201S, <italic>PHF2</italic> c.2678C>T p.S893L and <italic>ATL1</italic> c.1259A>C p.Q420P. Two of these mutations (<italic>ATL1</italic> and <italic>PHF2</italic>) 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 <italic>ATL1</italic> is likely the cause of early‐onset spastic paraplegia in this family.</p> </sec> <sec id="ncn372-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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 <italic>de novo</italic> mutations are suspected.</p> </sec> </abstract>