Apparent non-penetrance occurs in several genetic disorders, including tuberous sclerosis complex and neurofibromatosis type 1: clinically unaffected parents may have multiple affected offspring. Germ line or somatic mosaicism in one of the parents of the index patient is the probable cause and results in an enhanced recurrence risk. Therefore, it is of great importance to use the most sensitive technology for testing DNA of the parents of the index patient for the presence/absence of the familial mutation. To detect large rearrangements multiplex ligation-depending probe amplification (MLPA) is often used. Here we show that MLPA is less sensitive in detecting low-grade somatic mosaicism than fluorescence in situ hybridization (FISH) or a mutation-specific PCR test. Therefore, we recommend FISH (if possible) or PCR analysis for the analysis of parental DNA.

FISH, MLPA, mosaicism, mutation-specific PCR test, recurrence risk, sensitivity,
European Journal of Human Genetics
Erasmus MC: University Medical Center Rotterdam

van Veghel-Plandsoen, M, Wouters, C.H, Kromosoeto, J.N.R, den Ridder-Klünnen, M.C, Halley, D.J.J, & van den Ouweland, A.M.W. (2011). Multiplex ligation-depending probe amplification is not suitable for detection of low-grade mosaicism. European Journal of Human Genetics, 19(9), 1009–1012. doi:10.1038/ejhg.2011.60