Somatic Mosaicism of PCDH19 Mutation in a Family with Low-penetrance EFMR

The occurrence of epilepsy with mental retardation limited to females (EFMR; MIM 300088) has been recently associated to mutations in the PCDH19 gene, located on chromosome X and encoding for protocadherin 19. EFMR shows a rare X-linked inheritance wherein affected females may be segregating a mutation through unaffected transmitting males (Fabisiak and Erickson Clin Genet 38(5):353-358, 1990; Juberg and Hellman J Pediatr 79:726-732, 1971; Ryan et al. Nat Genet 17(1):92-95, 1997). The description of a pedigree segregating PCDH19 mutations from unaffected mothers to patients (Depienne et al. Hum Mutat 32:E1959-1975, 2011; Dibbens et al. Neurology 76:1514-1519, 2011) complicates disease inheritance and genetic counseling. In the present study, we describe a PCDH19 mutation segregating from an asymptomatic mother to an EFMR patient. In order to correlate the healthy phenotype with the genotype of the transmitting mother, we quantified in a few tissues the level of the mutant allele by real-time PCR, disclosing a somatic mosaicism. This finding has a great impact on genetic counseling.