title: Somatic mosaicism of PCDH19 mutation in a family with low-penetrance EFMR.
abstract: 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.
authors.affiliation: Unit of Molecular Medicine for Neuromuscular and Neurodegenerative diseases, Department of Neurosciences, Bambino Gesu' Children's Hospital, IRCCS, Rome, Italy. aaterracciano@yahoo.it
authors.forename: A
authors.initials: A
authors.lastname: Terracciano
authors.forename: N
authors.initials: N
authors.lastname: Specchio
authors.forename: F
authors.initials: F
authors.lastname: Darra
authors.forename: A
authors.initials: A
authors.lastname: Sferra
authors.forename: B Dalla
authors.initials: BD
authors.lastname: Bernardina
authors.forename: F
authors.initials: F
authors.lastname: Vigevano
authors.forename: E
authors.initials: E
authors.lastname: Bertini
mesh_terms: D000328:Adult; D015820:Cadherins / Q000235:genetics*; D002648:Child; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D050172:Genes, X-Linked; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D009030:Mosaicism; D020125:Mutation, Missense; D010375:Pedigree; D019683:Penetrance; D000091363:Protocadherins; D017422:Sequence Analysis, DNA
chemical_list: D015820:Cadherins; C438605:PCDH19 protein, human; D000091363:Protocadherins