オオトモ　タカノブ   Takanobu Otomo   大友　孝信    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   教授
論文種別	症例報告
言語種別	日本語
査読の有無	査読あり
表題	[A case of spastic paraplegia 48 with a novel mutation in the AP5Z1 gene].
掲載誌名	正式名：Rinsho shinkeigaku = Clinical neurology 略　 称：Rinsho Shinkeigaku ISSNコード：18820654/0009918X
掲載区分	国内
巻・号・頁	60(8),543-548頁
著者・共著者	Maruta Kyoko, Ando Masahiro, Otomo Takanobu, Takashima Hiroshi
発行年月	2020/08
概要	We describe an additional patient with spastic paraplegia 48 (SPG48). A 52-year-old woman with gradually increasing gait disturbance was admitted to our hospital. When she was 47 years old, acquaintances noted a shuffling gait. Gait worsening was evident at 48 years. Spastic gait was apparent at 50, and she required a walking stick at 54. Her elder brother had similar gait disturbance. No consanguinity was known. Neurologic examination at 52 disclosed spasticity and moderate weakness in the lower limbs. Spasticity and brisk reflexes in all limbs. Laboratory studies including HTLV-1 titer detected no abnormalities. MRI demonstrated mild corpus callosum narrowing and prominent anterior periventricular hyperintensities in fluid attenuation inversion recovery images. In limb muscles, electromyography (EMG) showed a chronic neurogenic pattern including reduced interference. Gene analysis identified compound homozygosity in exon 7 of adaptor-related protein complex 5 subunit zeta 1 (AP5Z1), including a novel frameshift mutation, c.1662_1672del;p.Glu554Hfs*15 in the patient, and a heterozygous missense mutation in asymptomatic family members, including her mother, two siblings, and a daughter. The frameshift mutation is considered a pathogenic variant according to American College of Medical Genetics and Genomics standards and guidelines. Based on clinical features, imaging findings and genetic abnormalities, we diagnosed this patient with SPG48. Mutations in AP5Z1, which encodes the ζ subunit of AP-5, underlie SPG48. The AP-5 adaptor protein complex, which is mutated in SPG48, binds to both spastizin and spatacsin. While hereditary spastic paraplegias generally are clinically and genetically heterogenous, SPG48, SPG11, and SPG15 are clinically similar.
DOI	10.5692/clinicalneurol.60.cn-001419
PMID	32641631