Original Paper

Identification of Two Novel Mutations in the Hydroxymethylbilane Synthase Gene in Three Patients from Two Unrelated Families with Acute Intermittent Porphyria
Patricia M.L. Ong^a, W. George Lanyon^a, Richard J. Hift^b, Janet Halkett^b, Celia E. Cramp^c, Michael R. Moore^d, J. Michael Connor<sup>a

a</sup> Duncan Guthrie Institute of Medical Genetics, Yorkhill, Glasgow, UK;
^b MRC/UCT Liver Research Centre, Cape Town, Republic of South Africa;
^c St. Helens and Knowsley Hospitals, Paediatric Department, Whiston Hospital, Prescot, Merseyside, UK;
^d National Research Centre for Environmental Toxicology, The University of Queensland, Coopers Plains, Australia

Address of Corresponding Author

Hum Hered 1998;48:24-29 (DOI: 10.1159/000022777)

  Key Words

• Hydroxymethylbilane synthase
• Acute intermittent porphyria
• CpG dinucleotide

  Abstract

We have screened the hydroxymethylbilane synthase cDNAs of 3 patients from 2 families suffering from acute intermittent porphyria (AIP) from Scotland and South Africa using heteroduplex and chemical cleavage of mismatch analyses. Direct sequencing was used to characterise the mutations. The two novel mutations identified were a missense mutation at nucleotide position 64 in exon 3 (R22C) and a single base-pair deletion in exon 15. These mutations are predicted to affect the normal function of the enzyme and, therefore, are expected to be the primary cause of disease in these patients.

  Author Contacts

Dr. Patricia M.L. Ong
Montreal Children's Hospital Research Institute
4060 Ste Catherine West, Room 242, Montréal, Qué. H3Z 2Z3 (Canada)
Tel. +1 514 934 4400 ext. 3281, Fax +1 514 934 4331
E-Mail cypo@musica.mcgill.ca

  Article Information

Received: Received: November 22, 1996
Revision received: July 21, 1997
Accepted: August 7, 1997
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 0, Number of References : 18