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. 2024 Dec 28;24(1):20.
doi: 10.1007/s12311-024-01782-y.

A Japanese Family with a Novel Pathogenic Variant in KIF1A Presenting with Spastic Paraparesis, Cerebellar Ataxia, and Intellectual Disability

Akihiko Mitsutake  1   2 , Mizuho Kawai  3 , Kenta Orimo  3   4 , Takashi Matsukawa  4 , Hiroyuki Ishiura  4   5 , Jun Mitsui  6 , Hideki Nakajima  3   7 , Hiroyuki Murai  3   8 , Shoji Tsuji  6   9 , Jun Goto  3   10 , Nobue K Iwata  3
Affiliations

A Japanese Family with a Novel Pathogenic Variant in KIF1A Presenting with Spastic Paraparesis, Cerebellar Ataxia, and Intellectual Disability

Akihiko Mitsutake et al. Cerebellum. .

Abstract

Variants in KIF1A are associated with hereditary spastic paraplegia (SPG30), which can manifest in both pure and complex forms. We describe a Japanese family with a novel KIF1A variant presenting with a complex form of SPG30. Patient 1, a 69-year-old woman, experienced progressive gait disturbance due to spastic paraparesis and cerebellar atrophy, and intellectual disability. Patient 2, the daughter of Patient 1, exhibited similar symptoms with more severe dysarthria. Patients 1 and 2 shared a heterozygous c.173 C > G (p.Ser58Trp) variant in the motor domain of KIF1A (NM_001244008.2), which is classified as likely pathogenic. This family highlights the role of autosomal dominant inheritance in a complex form of SPG30, expanding the understanding of its genetic basis and clinical presentation.

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Conflict of interest statement

Declarations. Ethics Approval: This study was approved by the institutional review board of the University of Tokyo. The patients provided written informed consent for the study and publication of this paper. Competing Interests: The authors declare no competing interests. Conflict of Interest: The authors declare no competing interests.

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