Carrier detection and phenotypic expression in a family with hereditary coproporphyria

Publication Type:
Thesis
Issue Date:
2007
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Introduction: Hereditary coproporphyria (HCP) is an autosomal dominant disorder that results from defects in the enzyme coproporphyrinogen oxidase (CPOX). A major clinical feature is neurologic damage that leads to peripheral and autonomic neuropathies and psychiatric manifestations, accompanied occasionally by cutaneous skin lesions. Hep symptoms are usually triggered by environmental factors such as drugs and hormones. However, the penetrance is low meaning that m.ost patients remain asymptomatic most of their lives. This makes it more difficult to diagnose asymptomatic HCP patients by solely relying on biochemical methods. The aim of this study was to genetically screen carriers in a family with Hep and design a questionnaire to identify subtle porphyria symptoms. Methods: Mutation screening was carried out in a family of thirty members, two of whom were symptomatic for HCP. The entire CPOX gene of the proband was screened for mutations. A questionnaire was designed and completed by 26 participants to review the clinical picture and life style of patients and was compared with the genetic data. Results: A novel mutation was identified in exon 5 at c.1064A>C causing a substitution in amino acid 355 from glutamine to proline (p.Q355P). Sequencing results revealed that sixteen out of thirty members of this family were carriers of the mutation. Porphyria related symptoms were noted to be as common in males as in females with the mutation. Conclusions: Patients with the Q355P mutation reported more symptoms than those without the mutation. Females reportedly are more likely to exhibit acute porphyria symptoms due to hormonal factors. However, it was noted that the number of symptoms reported by males with the mutation was more than that reported by females with the mutation. In this small sample cohort, these results suggest that environmental factors rather than endocrine factors play a role in the phenotypic expression of this mutation. Carriers are at risk of acute attacks; identifying them is beneficial because they can be given prior advice of preventative measures.
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