Human glycine decarboxylase gene (GLDC) and its highly conserved processed pseudogene (ψGLDC): Their structure and expression, and the identification of a large deletion in a family with nonketotic hyperglycinemia

Masaru Takayanagi, Shigeo Kure, Yoshiyuki Sakata, Yukiko Kurihara, Yukihiro Ohya, Mitsuharu Kajita, Keiya Tada, Yoichi Matsubara, Kuniaki Narisawa

研究成果: Article査読

30 被引用数 (Scopus)

抄録

Mutations in the glycine decarboxylase gene (GLDC) cause nonketotic hyperglycinemia (NKH), an inborn error of metabolism characterized by severe neurological disturbance. We have determined the structure of GLDC and of its pseudogene (ψGLDC) and studied their expression for a molecular analysis of NKH. The GLDC gene spans at least 135 kb and consists of 25 exons. All donor and acceptor sites adhere to the canonical GT-AG rule, except for the donor site of intron 21, where a variant form GC is used instead of GT. The transcription initiation site has been assigned to a residue 163 bp upstream from the translation initiation triplet by primer extension analysis. The ψGLDC gene has no intron and shares 97.5% homology with the coding region of functional GLDC, suggesting that ψGLDC is a processed pseudogene that arose from the GLDC transcript about 4-8 million years ago. RNA blotting analysis has revealed that GLDC is expressed in human liver, kidney, brain, and placenta. We have also examined a patient with NKH with no detectable GLDC mRNA in his lymphoblasts. Exons 1-3 of the functional GLDC gene from this patient are not amplified by polymerase chain reaction (PCR), whereas those from control subjects are. These results suggest a large homozygous deletion (at least 30 kb) in the patient. Furthermore, we have devised a semi-quantitative PCR to estimate the number of GLDC alleles by using ψGLDC as an internal control and have confirmed the homozygosity and heterozygosity of the deletion in the patient and his parents, respectively. Structural information of GLDC and ψGLDC should facilitate the molecular analysis of NKH.

本文言語English
ページ(範囲)298-305
ページ数8
ジャーナルHuman Genetics
106
3
DOI
出版ステータスPublished - 2000

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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