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Primary hyperoxaluria type 1 and brachydactyly mental retardation syndrome caused by a novel mutation in AGXT and a terminal deletion of chromosome 2

Authors

  • Rachaneekorn Tammachote,

    1. Faculty of Science, Human Genetics Research, Department of Botany, Chulalongkorn University, Bangkok, Thailand
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  • Nelawat Kingsuwannapong,

    1. Faculty of Science, Human Genetics Research, Department of Botany, Chulalongkorn University, Bangkok, Thailand
    2. Faculty of Medicine, Center of Excellence for Medical Genetics, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand
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  • Siraprapa Tongkobpetch,

    1. Faculty of Medicine, Center of Excellence for Medical Genetics, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand
    2. Excellence Center for Molecular Genetics, King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand
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  • Chalurmpon Srichomthong,

    1. Faculty of Medicine, Center of Excellence for Medical Genetics, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand
    2. Excellence Center for Molecular Genetics, King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand
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  • Patra Yeetong,

    1. Faculty of Medicine, Center of Excellence for Medical Genetics, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand
    2. Excellence Center for Molecular Genetics, King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand
    3. Faculty of Graduate School, Interdepartment of Biomedical Sciences, Chulalongkorn University, Bangkok, Thailand
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  • Pornchai Kingwatanakul,

    1. Faculty of Medicine, Division of Nephrology, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand
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  • Carla G. Monico,

    1. Division of Nephrology, Department of Internal Medicine and the Mayo Clinic Hyperoxaluria Center, Mayo Clinic, Rochester, Minnesota
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  • Kanya Suphapeetiporn,

    Corresponding author
    1. Faculty of Medicine, Center of Excellence for Medical Genetics, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand
    2. Excellence Center for Molecular Genetics, King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand
    • Head of Division of Medical Genetics and Metabolism, Department of Pediatrics, Sor Kor Building 11th floor, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand.
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  • Vorasuk Shotelersuk

    1. Faculty of Medicine, Center of Excellence for Medical Genetics, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand
    2. Excellence Center for Molecular Genetics, King Chulalongkorn Memorial Hospital, Thai Red Cross, Bangkok, Thailand
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  • How to Cite this Article: Tammachote R, Kingsuwannapong N, Tongkobpetch S, Srichomthong C, Yeetong P, Kingwatanakul P, Monico CG, Suphapeetiporn K, Shotelersuk V. 2012. Primary hyperoxaluria type 1 and brachydactyly mental retardation syndrome caused by a novel mutation in AGXT and a terminal deletion of chromosome 2. Am J Med Genet Part A. 158A:2124–2130.

Abstract

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder caused by mutations in the alanine:glyoxylate aminotransferase (AGXT) gene, located on chromosome 2q37. Mutant AGXT leads to excess production and excretion of oxalate, resulting in accumulation of calcium oxalate in the kidney, and progressive loss of renal function. Brachydactyly mental retardation syndrome (BDMR) is an autosomal dominant disorder, caused by haploinsufficiency of histone deacetylase 4 (HDAC4), also on chromosome 2q37. It is characterized by skeletal abnormalities and developmental delay. Here, we report on a girl who had phenotypes of both PH1 and BDMR. PCR-sequencing of the coding regions of AGXT showed a novel missense mutation, c.32C>G (p.Pro11Arg) inherited from her mother. Functional analyses demonstrated that it reduced the enzymatic activity to 31% of the wild-type and redirected some percentage of the enzyme away from the peroxisome. Microsatellite and array-CGH analyses indicated that the proband had a paternal de novo telomeric deletion of chromosome 2q, which included HDAC4. To our knowledge, this is the first report of PH1 and BDMR, with a novel AGXT mutation and a de novo telomeric deletion of chromosome 2q. © 2012 Wiley Periodicals, Inc.

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