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?
Germline mosaicism, also called gonadal mosaicism, is a type of genetic mosaicismwhere more than one set of genetic information is found specifically within the gamete cells. Germline mosaicism can be present at the same time as somatic mosaicism or individually depending on when the conditions occur. Pure germline mosaicism refers to mosaicism found exclusively in the gametes and not in any somatic cells. Germline mosaicism can be caused either by a mutation that occurs after conception, or by epigenetic regulation,alterations to DNA such as methylation that do not involve changes in the DNA coding sequence. A mutation in an allele acquired by a somatic cell early in its development can be passed on to its daughter cells, including those that later specialize to gametes. With such mutation within the gamete cells, a pair of medically typical individuals may have repeated succession of children who suffer from ceain genetic disorders such as Duchenne muscular dystrophyand osteogenesis imperfectabecause of germline mosaicism.It is possible for parents unaffected by germline mutations to produce an offspring with an autosomal dominant (AD) disorder due to a random new mutation within one's gamete cells known as sporadic mutation; however, if these parents produce more than one child with an AD disorder, germline mosaicism is more likely the cause than a sporadic mutation.In the first documented case of its kind, two offspring of a French woman who had no phenotypic expression of the AD disorder, hyperophic cardiomyopathy, inherited the disease. Ref Robbins 9/e pg 264
Non penetrance
Uniparental cliasomy
Genomic imprinting
Germline mosaicism
General pathology