Open Access

Application of multiplex ligation-dependent probe amplification, and identification of a heterozygous Alu-associated deletion and a uniparental disomy of chromosome 1 in two patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency

  • Authors:
    • Yuka Aoyama
    • Toshiyuki Yamamoto
    • Naomi Sakaguchi
    • Mika Ishige
    • Toju Tanaka
    • Tomoko Ichihara
    • Katsuaki Ohara
    • Hiroko Kouzan
    • Yasutomi Kinosada
    • Toshiyuki Fukao
  • View Affiliations

  • Published online on: April 14, 2015     https://doi.org/10.3892/ijmm.2015.2184
  • Pages: 1554-1560
  • Copyright: © Aoyama et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) deficiency is an autosomal recessive disorder affecting the leucine catabolic pathway and ketone body synthesis, and is clinically characterized by metabolic crises with hypoketotic hypoglycemia, metabolic acidosis and hyperammonemia. In the present study, we initially used PCR with genomic followed by direct sequencing to investigate the molecular genetic basis of HMGCL deficiency in two patients clinically diagnosed with the condition. Although we identified a mutation in each patient, the inheritance patterns of these mutations were not consistent with disease causation. Therefore, we investigated HMGCL using multiplex ligation‑dependent probe amplification (MLPA) to determine the copy numbers of all exons. A heterozygous deletion that included exons 2-4 was identified in one of the patients. MLPA revealed that the other patient had two copies for all HMGCL exons. Paternal uniparental isodisomy of chromosome 1 was confirmed in this patient by microarray analysis. These findings indicate that MLPA is useful for the identification of genomic aberrations and mutations other than small-scale nucleotide alterations. To the best of our knowledge, this is the first study describing HMGCL deficiency caused by uniparental disomy.
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June-2015
Volume 35 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Aoyama Y, Yamamoto T, Sakaguchi N, Ishige M, Tanaka T, Ichihara T, Ohara K, Kouzan H, Kinosada Y, Fukao T, Fukao T, et al: Application of multiplex ligation-dependent probe amplification, and identification of a heterozygous Alu-associated deletion and a uniparental disomy of chromosome 1 in two patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. Int J Mol Med 35: 1554-1560, 2015
APA
Aoyama, Y., Yamamoto, T., Sakaguchi, N., Ishige, M., Tanaka, T., Ichihara, T. ... Fukao, T. (2015). Application of multiplex ligation-dependent probe amplification, and identification of a heterozygous Alu-associated deletion and a uniparental disomy of chromosome 1 in two patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. International Journal of Molecular Medicine, 35, 1554-1560. https://doi.org/10.3892/ijmm.2015.2184
MLA
Aoyama, Y., Yamamoto, T., Sakaguchi, N., Ishige, M., Tanaka, T., Ichihara, T., Ohara, K., Kouzan, H., Kinosada, Y., Fukao, T."Application of multiplex ligation-dependent probe amplification, and identification of a heterozygous Alu-associated deletion and a uniparental disomy of chromosome 1 in two patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency". International Journal of Molecular Medicine 35.6 (2015): 1554-1560.
Chicago
Aoyama, Y., Yamamoto, T., Sakaguchi, N., Ishige, M., Tanaka, T., Ichihara, T., Ohara, K., Kouzan, H., Kinosada, Y., Fukao, T."Application of multiplex ligation-dependent probe amplification, and identification of a heterozygous Alu-associated deletion and a uniparental disomy of chromosome 1 in two patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency". International Journal of Molecular Medicine 35, no. 6 (2015): 1554-1560. https://doi.org/10.3892/ijmm.2015.2184