RESUMO
Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is caused by mutations in the gene PRRT2 located in 16p11.2. A deletion syndrome 16p11.2 is well established and is characterized by intellectual disability, speech delay, and autism. PKD/IC, however, is extremely rare in this syndrome. We describe a case of PKD/IC and 16p11.2 deletion syndrome and discuss modifiers of PRRT2 activity to explain the rare concurrence of both syndromes.
Assuntos
Transtorno Autístico/genética , Coreia/genética , Transtornos Cromossômicos/genética , Epilepsia Neonatal Benigna/genética , Deficiência Intelectual/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Transtorno Autístico/complicações , Criança , Coreia/etiologia , Deleção Cromossômica , Transtornos Cromossômicos/complicações , Cromossomos Humanos Par 16/genética , Distonia , Epilepsia Neonatal Benigna/etiologia , Genes Modificadores , Humanos , Deficiência Intelectual/complicações , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: A locus implicated in autosomal dominant cervical dystonia was assigned to chromosome 18p in 1 large family more than 15 years ago. This locus was designated DYT7. We reanalyzed the family clinically and genetically. METHODS: Clinical reevaluation of all family members was performed. There was Sanger sequencing of candidate genes, SNP array analysis, and exome sequencing in definitely affected family members. RESULTS: Diagnosis of cervical dystonia was definite in 6 family members and possible in 12. Analysis of candidate genes in 18p revealed no alteration in definitely affected patients. There was no disease causing copy number variant in 18p. No potentially disease-causing mutations were detected in 18p by exome sequencing. The CIZ1 gene, mutated in some cases of cervical dystonia, was excluded. CONCLUSIONS: Location of DYT7 on 18p in autosomal dominant cervical dystonia is questionable. We demonstrate genetic heterogeneity of this form of dystonia.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 18/genética , Distonia Muscular Deformante/genética , Ligação Genética/genética , Mutação/genética , Torcicolo/genética , Distonia/congênito , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Linhagem , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: A 3.68 Mbp duplication of 8p23.1 defines the 8p23.1 duplication syndrome. The main features of this syndrome are developmental delay and/or learning problems. RESULTS: Here we present a patient with a 1.80 Mbp duplication in 8p23.1 and characteristic signs and symptoms of the syndrome, including delay of motor and speech development and intellectual disability. DISCUSSION: The case indicates that genes within this interval, in particular dosage sensitive genes SOX7 and TNKS1, and possibly MIR124-1 and MIR598 as well suffice to cause the pathognomonic features of the 8p23.1 duplication syndrome.