Clinical Characterization of 2 Siblings with a Homozygous SPAST Variant

Cruz-Camino, Héctor; Vázquez-Cantú, Mercedes; Vázquez-Cantú, Diana Laura; Santos-Guzmán, Jesús; Bandala-Jacques, Antonio; Gómez-Gutiérrez, René; Cantú-Reyna, Consuelo

doi:10.12659/ajcr.919463

Cited by 2 publications

(2 citation statements)

References 22 publications

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“…Previously, there have been two reports of homozygous variants in SPAST. One, with the nonsense mutation p.(Ser545Ter), which also reports a complex and severe form of the disease, 69 and another, with the mutation p.(Leu534Pro), who showed a pure spastic paraparesis at the age of 39. 70 The patient from our cohort and the previously reported patient with p.(Ser545Ter) presented with a more severe form of the disease, probably because they carried nonsense mutations, while the latter patient had a missense mutation.…”

Section: Discussionmentioning

confidence: 99%

Genetic, structural and clinical analysis of spastic paraplegia 4

Varghaei

Estiar

Ashtiani

et al. 2022

Parkinsonism & Related Disorders

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Section: Discussionmentioning

confidence: 99%

Genetic, structural and clinical analysis of spastic paraplegia 4

Varghaei

Estiar

Ashtiani

et al. 2022

Parkinsonism & Related Disorders

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“…Previously, there have been two reports of homozygous variants in SPAST . One, with the nonsense mutation p.(Ser545Ter), which also reports a complex and severe form of the disease, 26 and another, with the mutation p.(Leu534Pro), who showed a pure spastic paraparesis at the age of 39. 27 The patient from our cohort and the previously reported patient with p.(Ser545Ter) presented with a more severe form of the disease, probably because they carried nonsense mutations, while the latter patient had a missense mutation.…”

Section: Discussionmentioning

confidence: 99%

Genetic, structural and clinical analysis of spastic paraplegia 4

Varghaei

Estiar

Ashtiani

et al. 2021

Preprint

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Background: Spastic paraplegia type 4 (SPG4), resulting from heterozygous mutations in the SPAST gene, is the most common form among the heterogeneous group of hereditary spastic paraplegias (HSPs). Objective: To study genetic and clinical characteristics of SPG4 across Canada. Methods: The SPAST gene was analyzed in a total of 696 HSP patients from 431 families by either HSP-gene panel sequencing or whole exome sequencing (WES). We used Multiplex ligation-dependent probe amplification to analyze copy number variations (CNVs), and performed in silico structural analysis of selected mutations. Clinical characteristics of patients were assessed, and long-term follow-up was done to study genotype-phenotype correlations. Results: We identified 157 SPG4 patients from 65 families who carried 41 different SPAST mutations, six of which are novel and six are CNVs. We report novel aspects of mutations occurring in Arg499, a case with homozygous mutation, a family with probable compound heterozygous mutations, three patients with de novo mutations, three cases with pathogenic synonymous mutation, co-occurrence of SPG4 and multiple sclerosis, and novel or rarely reported signs and symptoms seen in SPG4 patients. Conclusion: Our study demonstrates that SPG4 is a heterogeneous type of HSP, with diverse genetic features and clinical manifestations. In rare cases, biallelic inheritance, de novo mutation, pathogenic synonymous mutations and CNVs should be considered.

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Clinical Characterization of 2 Siblings with a Homozygous SPAST Variant

Cited by 2 publications

References 22 publications

Genetic, structural and clinical analysis of spastic paraplegia 4

Genetic, structural and clinical analysis of spastic paraplegia 4

Genetic, structural and clinical analysis of spastic paraplegia 4

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