An asymptomatic 31-year-old woman (Consultant) is asymptomatic and has a 10-week gestation according to ultrasound study (primiparous). Her younger brother (index case) aged 26 years is affected by ataxia and genetically diagnosed as a heterozygous carrier of an expansive mutation of 70 CAG repeats in the SCA3 gene (chromosome 14). The patient is referred to the genetic counseling office where a possible chorionic villus biopsy to study the fetal genotype is evaluated. Is this invasive procedure indicated as a pre-natal diagnosis (PND) in this case?
SCA3 is Spinocerebellar Ataxia type 3 also called Machado-Joseph disease. It is caused by mutations in the ATXN3 gene by the CAG triplet repeat expansion mechanism. Affected individuals have between 52 and 86 CAG triplet repeats in heterozygosis with complete penetrance. The heterozygous mutation carrier has the disease as its inheritance pattern is autosomal dominant. In this clinical case, the one who has the disease and has the mutated gene in heterozygosis is the brother (26 years old) of the pregnant woman. I think that before doing the chorion biopsy, the pregnant woman should be tested to know her ATXN3 gene status. She has a 50% chance of carrying the mutation and having the disease, but since she is 31 years old, I think she should have already had symptoms. Nevertheless, I would do the genetic test on the pregnant woman to be on the safe side. If she came out without the mutation, there would be nothing more to do because the disease would no longer be transmitted. If she came out with the mutation, then I would do a chorionic villus biopsy. Answers 1 and 2 are both true, but I think answer 1 is more true than answer 2.
It is indicated after studying the Consultant's genotype and only if it is heterozygous.
This is not indicated, since SCA3 ataxia is full penetrance and the Consultant is asymptomatic and therefore has not inherited the mutation.
It may be indicated in the next pregnancy, after studying the genotype of the first child and detecting the mutation in it.
SCA3 ataxia is recessively inherited, so there is no appreciable risk of disease transmission and PND is not indicated.
This is indicated regardless of the Consultant's genotype, since SCA3 ataxia is maternally inherited (transmitted by women).
In this clinical case, the one who has the disease and has the mutated gene in heterozygosis is the brother (26 years old) of the pregnant woman. I think that before doing the chorion biopsy, the pregnant woman should be tested to know her ATXN3 gene status. She has a 50% chance of carrying the mutation and having the disease, but since she is 31 years old, I think she should have already had symptoms.