Pathology – MCQ 43 – Couple with two children affected with tuberous selerosis

A couple has two children affected with tuberous selerosis. On detailed clinical and laboratory evaluation (including molecular studies) both parents are normal. Which one of the following
explains the two affected children in this family?
a) Non penetrance
b) Uniparental disomy
c) Genomic imprinting
d) Germline mosaicism

Correct answer : d) Germline mosaicism

A person can be affected with tuberous sclerosis as a result of inheritance from the parents or as a result of spontaneous mutation. In tuberous sclerosis, the mode of inheritance is autosomal dominant. But in this case the parents is not affected with tuberous sclerosis. Hence autosomal dominant mode of inheritance cannot occur. In case of spontaneous mutation, one of the children of unaffected parents can have the disease. But in this case, 2 children have the disease. The same mutation to occur in both children at the same time is very rare! There is one another method by which a child may acquire the disease – Germline mosaicism in the parents. Mosaicism simply means that some of the cells of a person have a particular genetic mutation and the rest of the cells are normal. If the proportion of such cells is very low, the person will not exhibit the properties of the disease. But if some of his / her germ cells contain the mutated gene, it may get transmitted to the offspring. Thus, germline mosaicism can result in birth of more than one affected child to unaffected parents!