Late-onset spastic ataxia phenotype in a patient with a homozygous DDHD2 mutation

Doi, Hiroshi, Ushiyama, Masao, Baba, Takashi, Tani, Katsuko, Shiina, Masaaki, Ogata, Kazuhiro, Miyatake, Satoko, Fukuda-Yuzawa, Yoko, Tsuji, Shoji, Nakashima, Mitsuko, Tsurusaki, Yoshinori, Miyake, Noriko, Saitsu, Hirotomo, Ikeda, Shu-ichi, Tanaka, Fumiaki, Matsumoto, Naomichi, Yoshida, Kunihiro

doi:10.1038/srep07132

Autosomal recessive cerebellar ataxias and autosomal recessive hereditary spastic paraplegias (ARHSPs) are clinically and genetically heterogeneous neurological disorders. Herein we describe Japanese siblings with a midlife-onset, slowly progressive type of cerebellar ataxia and spastic paraplegia, without intellectual disability. Using whole exome sequencing, we identified a homozygous missense mutation in DDHD2, whose mutations were recently identified as the cause of early-onset ARHSP with intellectual disability. Brain MRI of the patient showed a thin corpus callosum. Cerebral proton magnetic resonance spectroscopy revealed an abnormal lipid peak in the basal ganglia, which has been reported as the hallmark of DDHD2-related ARHSP (SPG 54). The mutation caused a marked reduction of phospholipase A(1) activity, supporting that this mutation is the cause of SPG54. Our cases indicate that the possibility of SPG54 should also be considered when patients show a combination of adult-onset spastic ataxia and a thin corpus callosum. Magnetic resonance spectroscopy may be helpful in the differential diagnosis of patients with spastic ataxia phenotype.

Late-onset spastic ataxia phenotype in a patient with a homozygous DDHD2 mutation

Search this article

Description

Journal

Citations (6)*help

References(28)*help

Related Projects

Keywords

Details 詳細情報について

Export

Report a problem