Biochemical testing cannot be relied upon to identify individuals who are heterozygous for NPC gene mutations (carriers), because test results for such individuals are similar to those seen in controls. Molecular analysis of the NPC1 or NPC2 genes can be used to identify NPC carriers if NPC1 or NPC2 mutations have been found in an identified, affected family member.
Genetic counselling provides individuals and families affected by NPC with information on the nature, inheritance, and implications of this genetic disorder in order to help them make informed medical and personal decisions. It is particularly relevant with regard to family planning. The optimal time to determine genetic risk, clarify carrier status and discuss the availability of prenatal testing is before pregnancy.
Prenatal testing is provided to pregnant women where there is a 25% risk of NPC in the foetus. It is performed in either of two ways:1
1. Biochemical testing performed on foetal cells obtained by amniocentesis at 15–18 weeks of gestation, or by chorionic villus sampling (CVS) at 10–12 weeks’ gestation. This is only applicable if the affected individual from whom a family history has been ascertained (the proband) has a ‘classic’ biochemical phenotype, and is of no use when the proband has the ‘variant biochemical phenotype’.
2. Genetic testing performed on DNA extracted from foetal cells obtained by amniocentesis at 15–18 weeks of gestation, or by CVS at 10–12 weeks’ gestation. Molecular genetic analysis is only applicable if disease causing mutations in NPC1 or NPC2 have been identified in the proband, or if a family study has indicated linked genetic markers.
1. Vanier MT. Prenatal diagnosis of Niemann–Pick diseases types A, B and C. Prenat Diagn 2002;22:630–2.
© 2007 Blackwell Publishing Limited. Reproduced by permission.