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Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly
Author(s) -
Kato Mitsuhiro,
Nanba Eiji,
Akaboshi Shinjiro,
Shiihara Takashi,
Ito Aiko,
Honma Tomomi,
Tsuburaya Kenji,
Hayasaka Kiyoshi
Publication year - 2000
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(200004)47:4<514::aid-ana16>3.0.co;2-h
Subject(s) - sonic hedgehog , holoprosencephaly , missense mutation , exon , biology , genetics , mutation , microphthalmia , microbiology and biotechnology , gene , fetus , pregnancy
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. Ann Neurol 2000;47:514–516.