title: A new missense mutation found in the FLNA gene in a family with bilateral periventricular nodular heterotopia (BPNH) alters the splicing process.
abstract: We describe the clinical and molecular evaluation of two patients, mother and daughter (proband), with bilateral periventricular nodular heterotopia (BPNH). The clinical evaluation revealed a more severe phenotype in the proband, with mental retardation and seizures. Imaging studies showed bilateral periventricular nodules in both patients. We identified a novel mutation, c.987G-->C mutation in exon 6 of the Filamin A (FLNA) gene in the genomic DNA of both patients. Complementary DNA (cDNA) sequencing revealed the maintenance of intron 6 in the mutated allele. Bioinformatics analysis indicates that the mutation identified in both patients probably destroyed the intron 6 donor-splicing site, which is likely to introduce a premature stop codon resulting in a truncated FLNA protein. In addition, X-chromosome inactivation studies in DNA of blood cells revealed a skewed pattern in the proband, and real time quantitative polymerase chain reaction (PCR) showed a higher expression of the mutated allele in the proband compared to that of the mother. This variation in expression of the mutated allele may be responsible for the differences in the clinical manifestations observed in both patients.
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas - UNICAMP, Tessália Vieira de Camargo, 126, Campinas, SP, Brazil, 13084-971.
authors.forename: Simone S
authors.initials: SS
authors.lastname: Tsuneda
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Torres
authors.forename: Maria A
authors.initials: MA
authors.lastname: Montenegro
authors.forename: Marilisa M
authors.initials: MM
authors.lastname: Guerreiro
authors.forename: Fernando
authors.initials: F
authors.lastname: Cendes
authors.forename: Iscia
authors.initials: I
authors.lastname: Lopes-Cendes
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D018389:Codon, Nonsense / Q000235:genetics; D003285:Contractile Proteins / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics / Q000473:pathology; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D064448:Filamins; D006801:Humans; D007438:Introns / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D054091:Periventricular Nodular Heterotopia / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics*; D049951:X Chromosome Inactivation
chemical_list: D018389:Codon, Nonsense; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins