Human Genetics

, Volume 116, Issue 1, pp 114–120

A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia

  • Samuel Canizales-Quinteros
  • Carlos A. Aguilar-Salinas
  • Adriana Huertas-Vázquez
  • María L. Ordóñez-Sánchez
  • Maribel Rodríguez-Torres
  • José L. Venturas-Gallegos
  • Laura Riba
  • Salvador Ramírez-Jimenez
  • Rocío Salas-Montiel
  • Giovani Medina-Palacios
  • Ludivina Robles-Osorio
  • Angel Miliar-García
  • Luis Rosales-León
  • Blanca H. Ruiz-Ordaz
  • Alejandro Zentella-Dehesa
  • Adrian Ferré-D’Amare
  • Francisco J. Gómez-Pérez
  • Ma. Teresa. Tusié-Luna
Original Investigation

DOI: 10.1007/s00439-004-1192-9

Cite this article as:
Canizales-Quinteros, S., Aguilar-Salinas, C.A., Huertas-Vázquez, A. et al. Hum Genet (2005) 116: 114. doi:10.1007/s00439-004-1192-9

Abstract

Autosomal recessive hypercholesterolemia (ARH) is characterized by elevated LDL serum levels, xanthomatosis, and premature coronary artery disease. Three loci have been described for this condition (1p35, 15q25-q26 and 13q). Recently, the responsible gene at the 1p35 locus, encoding an LDL receptor adaptor protein (ARH) has been identified. We studied a Mexican ARH family with two affected siblings. Sequence analysis of the ARH gene (1p35 locus) revealed that the affected siblings are homozygous for a novel mutation (IVS4+2T>G) affecting the donor splice site in intron 4, whereas both the parents and an unaffected sister are heterozygous for this mutation. The IVS4+2T>G mutation results in a major alternative transcript derived from a cryptic splice site, which carries an in-frame deletion of 78 nucleotides in the mature mRNA. The translation of this mRNA yields a mutant protein product (ARH-26) lacking 26 amino acids, resulting in the loss of β-strands β6 and β7 from the PTB domain. This is the first case where a naturally occurring mutant with an altered PTB domain has been identified.

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Samuel Canizales-Quinteros
    • 1
  • Carlos A. Aguilar-Salinas
    • 2
  • Adriana Huertas-Vázquez
    • 1
  • María L. Ordóñez-Sánchez
    • 2
  • Maribel Rodríguez-Torres
    • 1
  • José L. Venturas-Gallegos
    • 3
  • Laura Riba
    • 1
  • Salvador Ramírez-Jimenez
    • 1
  • Rocío Salas-Montiel
    • 1
  • Giovani Medina-Palacios
    • 4
  • Ludivina Robles-Osorio
    • 2
  • Angel Miliar-García
    • 5
  • Luis Rosales-León
    • 4
  • Blanca H. Ruiz-Ordaz
    • 4
  • Alejandro Zentella-Dehesa
    • 3
  • Adrian Ferré-D’Amare
    • 6
  • Francisco J. Gómez-Pérez
    • 2
  • Ma. Teresa. Tusié-Luna
    • 1
  1. 1.Unidad de Biología Molecular y Medicina GenómicaInstituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán”Mexico CityMexico
  2. 2.Departamento de Endocrinología y Metabolismo de LípidosInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityMexico
  3. 3.Departamento de Biología Celular, Instituto de Fisiología CelularUniversidad Nacional Autónoma de MéxicoMexico CityMexico
  4. 4.Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoMexico CityMexico
  5. 5.Sección de Estudios de Posgrado e Investigación, Escuela Superior de MedicinaInstituto Politécnico NacionalMexico CityMexico
  6. 6.Division of Basic SciencesFred Hutchinson Cancer Research CenterSeattleUSA

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