Recurrence risk of epilepsy and mental retardation in females due to parental mosaicism of PCDH19 mutations

• DOI: 10.1212/wnl.0b013e318217e7b6
• Publication Date: 2011-04-25T20:33:04Z
• Authors: L.M. Dibbens; R. Kneen; M.A. Bayly; S.E. Heron; T. Arsov; J.A. Damiano; T. Desai; J. Gibbs; F. McKenzie; J.C. Mulley; A. Ronan; I.E. Scheffer
• Keywords: Germline mosaicism

Two unrelated families were ascertained in which sisters had infantile onset of epilepsy and developmental delay. Mutations the protocadherin 19 (PCDH19) gene cause mental retardation limited to females (EFMR). Despite both sister pairs having a PCDH19 mutation, neither parent each family was heterozygous carrier mutation. The possibility parental mosaicism mutations investigated.Genomic DNA from peripheral blood obtained sequenced for mutations. Parentage confirmed by markers.Both have mutation PCDH19. Sister pair 1 has missense c.74T>C, L25P, while sequence analysis indicates their parents are negative Diagnostic restriction enzyme detected low-level mother. 2 half-sisters who share mother c.1019 A>G, N340S. chromatograph shows reduced signal same These data indicate maternal somatic gonadal pairs. Phenotyping is suggestive of, detection diagnostic for, disorder EFMR affected girls.We show that an important molecular mechanism associated with inheritance EFMR. This should be considered when providing genetic counseling couples one daughter as they may risk recurrence daughters sons at transmitting