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 ?
Ans. is 'd' i.e. germline mosaicism Inheritance of Tuberous sclerosis o Tuberous sclerosis is a genetic condition which is transmitted either through inheritance or as a spontaneous genetic mutation. o Mutation in one of the two genes TSC1 and TSC2 have been identified as a cause for tuberous sclerosis. o Approximately 33% or one third of people with Tuberous sclerosis inherit it from a parent who also has tuberous sclerosis. This occurs dominance inheritance. o Thus there is 50 per cent chance with each pregnancy for a parent with Tuberous sclerosis to have a child with Tuberous sclerosis. o In the remaining 66 % or two thirds of the people with Tuberous sclerosis, neither parent has tuberous sclerosis. o It appears that one of the normal genes from either parent changes to the abnormal form, leading to a new (or sporadic), occurrence of tuberous sclerosis in the child. Normally these parents do not have another child with tuberous sclerosis because the mutation was sporadic not inherited. However, some families have more than one child with Tuberous sclerosis even though neither parent showed symptoms or findings of Tuberous sclerosis. How does this occur? o Scientists have determined that small number of physically unaffected parents of a child with TSC have mutations in some of their cells. o Because the mutation is limited to a small poion of all of the body's cells, these individuals show no signs of Tuberous sclerosis. o But if a poion of the egg or sperm cells of a parent carries the tuberous sclerosis mutation, that parent can have more than one affected child, possibly at the same 50/50 chance that people with Tuberous sclerosis have. o A person who carries cells with Tuberous sclerosis mutation in her egg or his sperm supply has germline mosaicism. o "Mosaicism" means that the person's body is made up of a combination of cells with and cells without a Tuberous sclerosis mutation. o 'Germline mosaicism' refers to the presence of cells with Tuberous sclerosis mutations in the egg or the sperm cell supply. o Germline mosaicism is relatively rare and this explanation does not apply to most families with a sporadically affected child. However, the occurrence of germline mosaicism has geneticists to estimate a recurrence risk (or chance that a family with a sporadically affected child will have anohter child with TSC) ranging from 1 to 3%. At this time there is no way to determine whether an unaffected parent of a child with TSC has germline mosaicism.
Non penetrance
Uniparental diasomy
Genomic imprinting
Germline mosaicism