title: Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly.
abstract: 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.
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: E
authors.initials: E
authors.lastname: Nanba
authors.forename: S
authors.initials: S
authors.lastname: Akaboshi
authors.forename: T
authors.initials: T
authors.lastname: Shiihara
authors.forename: A
authors.initials: A
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Honma
authors.forename: K
authors.initials: K
authors.lastname: Tsuburaya
authors.forename: K
authors.initials: K
authors.lastname: Hayasaka
mesh_terms: D000328:Adult; D061085:Agenesis of Corpus Callosum; D003337:Corpus Callosum / Q000737:chemistry; D053823:Hedgehog Proteins; D016142:Holoprosencephaly / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017354:Point Mutation; D021382:Protein Sorting Signals / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D015534:Trans-Activators
chemical_list: D053823:Hedgehog Proteins; D021382:Protein Sorting Signals; D011506:Proteins; C509239:SHH protein, human; D015534:Trans-Activators