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Detection of heterozygotes

  • Chapter
Medico-Social Management of Inherited Metabolic Disease

Abstract

An individual homozygous for a pathogenic recessive gene will have gross clinical or biochemical abnormalities which can usually be easily recognized. However, the heterozygote, carrying one abnormal (mutant) gene and one normal (wild-type) gene, will be, at least superficially, phenotypically normal because the normal gene ordinarily masks the presence of the abnormal gene. Some qualification with respect to the normality of heterozygotes is necessary because slight clinical manifestations, collectively recognizable but in the individual difficult to distinguish from the normal variation are known in some diseases and are suspected in others. These are more common in the sex-linked inherited metabolic diseases such as glucose-6-phosphate dehydrogenase deficiency, where the female carrier may have increased susceptibility to drug-induced anaemia1 or Fabry’s disease, where the carrier may have corneal opacity.2 This may be explicable in terms of sex-chromosome inactivation (discussed later), but there are examples for autosomally inherited diseases. Electroencephalographic abnormalities in phenylketonuria heterozygotes have occasionally been noted3,4 and Gaucher cells have been found in the bone marrow of healthy relatives of patients with Gaucher’s disease.5

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  1. Department of Clinical Chemistry, The Children’s Hospital, Ladywood Middleway, Birmingham, B16 8ET, UK

    D. N. Raine

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Westwood, A. (1977). Detection of heterozygotes. In: Raine, D.N. (eds) Medico-Social Management of Inherited Metabolic Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-6173-2_12

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