Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly
| Autor: | Aiko Ito, Mitsuhiro Kato, Kiyoshi Hayasaka, Takashi Shiihara, Shinjiro Akaboshi, Tomomi Honma, Eiji Nanba, Kenji Tsuburaya |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Signal peptide Nonsense mutation Protein Sorting Signals Biology medicine.disease_cause Corpus Callosum Exon Holoprosencephaly medicine Humans Point Mutation Missense mutation Hedgehog Proteins Sonic hedgehog Genetics Mutation Proteins medicine.disease Magnetic Resonance Imaging Neurology Trans-Activators biology.protein Neurology (clinical) Agenesis of Corpus Callosum Haploinsufficiency |
| Zdroj: | Annals of Neurology. 47:514-516 |
| ISSN: | 1531-8249 0364-5134 |
| DOI: | 10.1002/1531-8249(200004)47:4<514::aid-ana16>3.0.co;2-h |
| Popis: | We investigated the molecular basis of holoprosencephaly in a sporadic patient and identified a novel missense mutation in the signal sequence of the sonic hedgehog (Shh) gene. Magnetic resonance imaging of the head showed a lobar type of holoprosencephaly and partial agenesis of the anterior corpus callosum. He was treated for craniosynostosis at 7 months of age. All three exons of the Shh gene were amplified by polymerase chain reaction from genomic DNA of the patient and controls. Sequencing analysis of the polymerase chain reaction fragments, screened by single-strand conformation polymorphism analysis, revealed a heterozygous mutation of a T-to-C substitution at nucleotide position 50. This mutation predicted an amino acid replacement of leucine to proline at codon 17 located in the signal peptide of SHH protein. It probably disturbs the translocation of the protein into the endoplasmic reticulum and may lead to holoprosencephaly because of haploinsufficiency of Shh. |
| Databáze: | OpenAIRE |
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