KIF5A and ALS2 Variants in a Family With Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis

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Abstract

This paper describes the clinical evolution and the novel genetic findings in a KIF5A mutated family previously reported as affected by spastic paraparesis only. The additional evidence we report here, a homozygous ALS2 mutation detected in the proband, and the clinical evolution observed in the affected members of the family, are in line with the evidence of an overlap between Hereditary Spastic Paraplegias and Amyotrophic Lateral Sclerosis associated with variants in these genes. The proband, a 14-years-old boy, started manifesting a pure form of HSP at age 14 months. The disease rapidly progressed to a juvenile form of ALS. This boy carries a heterozygous missense variant in KIF5A p.(Glu755Lys), inherited from the father, and a homozygous missense variant in the alsin protein encoded by the ALS2 gene p.(Pro192Leu). The father shows a family history of ALS. In the last few years, he has been developing signs and symptoms of both upper and lower motor neuron degeneration, with mild bulbar motor involvement and emotional lability. The patients described in this family, confirm the continuum and partial overlap of the two clinical entities, HSP and ALS, historically viewed as distinct entities. The genetic findings in this family further substantiate the genetic bases underlying the overlap, broadening the clinical spectrum associated with KIF5A mutations.

Original languageEnglish
Pages (from-to)1078
Number of pages5
JournalFrontiers in Neurology
Volume9
DOIs
Publication statusPublished - 2018

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Hereditary Spastic Paraplegia
Amyotrophic Lateral Sclerosis
Fathers
Spastic Paraparesis
Nerve Degeneration
Mutation
Molecular Evolution
Motor Neurons
Genes
Signs and Symptoms
Juvenile Amyotrophic Lateral Sclerosis 2
Proteins

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@article{8fc67d726329476db96bbad8639ce66e,
title = "KIF5A and ALS2 Variants in a Family With Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis",
abstract = "This paper describes the clinical evolution and the novel genetic findings in a KIF5A mutated family previously reported as affected by spastic paraparesis only. The additional evidence we report here, a homozygous ALS2 mutation detected in the proband, and the clinical evolution observed in the affected members of the family, are in line with the evidence of an overlap between Hereditary Spastic Paraplegias and Amyotrophic Lateral Sclerosis associated with variants in these genes. The proband, a 14-years-old boy, started manifesting a pure form of HSP at age 14 months. The disease rapidly progressed to a juvenile form of ALS. This boy carries a heterozygous missense variant in KIF5A p.(Glu755Lys), inherited from the father, and a homozygous missense variant in the alsin protein encoded by the ALS2 gene p.(Pro192Leu). The father shows a family history of ALS. In the last few years, he has been developing signs and symptoms of both upper and lower motor neuron degeneration, with mild bulbar motor involvement and emotional lability. The patients described in this family, confirm the continuum and partial overlap of the two clinical entities, HSP and ALS, historically viewed as distinct entities. The genetic findings in this family further substantiate the genetic bases underlying the overlap, broadening the clinical spectrum associated with KIF5A mutations.",
author = "Marta Simone and Antonio Trabacca and Elena Panzeri and Luciana Losito and Andrea Citterio and Bassi, {Maria Teresa}",
year = "2018",
doi = "10.3389/fneur.2018.01078",
language = "English",
volume = "9",
pages = "1078",
journal = "Frontiers in Neurology",
issn = "1664-2295",
publisher = "Frontiers Research Foundation",

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TY - JOUR

T1 - KIF5A and ALS2 Variants in a Family With Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis

AU - Simone, Marta

AU - Trabacca, Antonio

AU - Panzeri, Elena

AU - Losito, Luciana

AU - Citterio, Andrea

AU - Bassi, Maria Teresa

PY - 2018

Y1 - 2018

N2 - This paper describes the clinical evolution and the novel genetic findings in a KIF5A mutated family previously reported as affected by spastic paraparesis only. The additional evidence we report here, a homozygous ALS2 mutation detected in the proband, and the clinical evolution observed in the affected members of the family, are in line with the evidence of an overlap between Hereditary Spastic Paraplegias and Amyotrophic Lateral Sclerosis associated with variants in these genes. The proband, a 14-years-old boy, started manifesting a pure form of HSP at age 14 months. The disease rapidly progressed to a juvenile form of ALS. This boy carries a heterozygous missense variant in KIF5A p.(Glu755Lys), inherited from the father, and a homozygous missense variant in the alsin protein encoded by the ALS2 gene p.(Pro192Leu). The father shows a family history of ALS. In the last few years, he has been developing signs and symptoms of both upper and lower motor neuron degeneration, with mild bulbar motor involvement and emotional lability. The patients described in this family, confirm the continuum and partial overlap of the two clinical entities, HSP and ALS, historically viewed as distinct entities. The genetic findings in this family further substantiate the genetic bases underlying the overlap, broadening the clinical spectrum associated with KIF5A mutations.

AB - This paper describes the clinical evolution and the novel genetic findings in a KIF5A mutated family previously reported as affected by spastic paraparesis only. The additional evidence we report here, a homozygous ALS2 mutation detected in the proband, and the clinical evolution observed in the affected members of the family, are in line with the evidence of an overlap between Hereditary Spastic Paraplegias and Amyotrophic Lateral Sclerosis associated with variants in these genes. The proband, a 14-years-old boy, started manifesting a pure form of HSP at age 14 months. The disease rapidly progressed to a juvenile form of ALS. This boy carries a heterozygous missense variant in KIF5A p.(Glu755Lys), inherited from the father, and a homozygous missense variant in the alsin protein encoded by the ALS2 gene p.(Pro192Leu). The father shows a family history of ALS. In the last few years, he has been developing signs and symptoms of both upper and lower motor neuron degeneration, with mild bulbar motor involvement and emotional lability. The patients described in this family, confirm the continuum and partial overlap of the two clinical entities, HSP and ALS, historically viewed as distinct entities. The genetic findings in this family further substantiate the genetic bases underlying the overlap, broadening the clinical spectrum associated with KIF5A mutations.

U2 - 10.3389/fneur.2018.01078

DO - 10.3389/fneur.2018.01078

M3 - Article

C2 - 30581417

VL - 9

SP - 1078

JO - Frontiers in Neurology

JF - Frontiers in Neurology

SN - 1664-2295

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