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2 results on '"Splice site donor mutation"'

1. Late-onset spastic paraplegia: Aberrant SPG11 transcripts generated by a novel splice site donor mutation.

Author

Kawarai, Toshitaka, Miyamoto, Ryosuke, Mori, Atsuko, Oki, Ryosuke, Tsukamoto-Miyashiro, Ai, Matsui, Naoko, Miyazaki, Yoshimichi, Orlacchio, Antonio, Izumi, Yuishin, Nishida, Yoshihiko, and Kaji, Ryuji

Subjects
*PARAPLEGIA, *SPASTICITY, *GENETIC transcription, *GENETIC mutation, *JAPANESE people, *THERAPEUTICS, *DISEASES
Abstract

We identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866 + 1G > A) in consanguineous Japanese SPG11 siblings showing late-onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus . Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis. [ABSTRACT FROM AUTHOR]

Published
2015
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2. Late-onset spastic paraplegia: Aberrant SPG11 transcripts generated by a novel splice site donor mutation

Author

Yoshihiko Nishida, Ryuji Kaji, Naoko Matsui, Ryosuke Oki, Antonio Orlacchio, Ryosuke Miyamoto, Ai Tsukamoto-Miyashiro, Yuishin Izumi, Atsuko Mori, Toshitaka Kawarai, and Yoshimichi Miyazaki

Subjects
Adult, Male, Hereditary spastic paraplegia, Nonsense-mediated decay, DNA Mutational Analysis, Nonsense-mediated mRNA decay, Biology, DNA sequencing, Exon, Aberrant transcript, medicine, Humans, splice, Exome sequencing, Spastic paraplegia, SPG11, Splice site donor mutation, Whole-exome sequencing, Neurology (clinical), Neurology, Genetics, Family Health, Paraplegia, Splice site mutation, Intron, Proteins, medicine.disease, Molecular biology, Magnetic Resonance Imaging, Introns, Mutation, Female, Settore MED/26 - Neurologia
Abstract

We identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866 + 1G > A) in consanguineous Japanese SPG11 siblings showing late-onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis.

Published
2015

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