Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Análise Mutacional de DNA/métodos , Proteínas de Ligação a DNA , Mutação em Linhagem Germinativa/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Adaptadoras de Transdução de Sinal , Países Bálticos/epidemiologia , Proteínas de Transporte , Humanos , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas Nucleares , Polônia/epidemiologiaRESUMO
We reported four cases of Hallervorden-Spatz disease. All four siblings (three males and one female) in the family are affected. The first symptoms of the disease were spastic paraparesis and optic atrophy followed by trunkal dystonia and lower motor neurone involvement. The average age of the onset was 4.25 years. The diagnosis was made at the ages of 17, 14, 11 and 10 years. The diagnosis was confirmed clinically, electrophysiologically and by MRI. On MRI scans all patients demonstrated hypointense areas in globus pallidus. There is neither specific treatment nor prenatal diagnosis.
Assuntos
Espasticidade Muscular/diagnóstico , Atrofias Ópticas Hereditárias/diagnóstico , Neurodegeneração Associada a Pantotenato-Quinase/diagnóstico , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Espasticidade Muscular/etiologia , Espasticidade Muscular/genética , Núcleo Familiar , Atrofias Ópticas Hereditárias/etiologia , Atrofias Ópticas Hereditárias/genética , Neurodegeneração Associada a Pantotenato-Quinase/complicações , Neurodegeneração Associada a Pantotenato-Quinase/genéticaRESUMO
The CCR5-Delta32 deletion obliterates the CCR5 chemokine and the human immunodeficiency virus (HIV)-1 coreceptor on lymphoid cells, leading to strong resistance against HIV-1 infection and AIDS. A genotype survey of 4,166 individuals revealed a cline of CCR5-Delta32 allele frequencies of 0%-14% across Eurasia, whereas the variant is absent among native African, American Indian, and East Asian ethnic groups. Haplotype analysis of 192 Caucasian chromosomes revealed strong linkage disequilibrium between CCR5 and two microsatellite loci. By use of coalescence theory to interpret modern haplotype genealogy, we estimate the origin of the CCR5-Delta32-containing ancestral haplotype to be approximately 700 years ago, with an estimated range of 275-1,875 years. The geographic cline of CCR5-Delta32 frequencies and its recent emergence are consistent with a historic strong selective event (e.g. , an epidemic of a pathogen that, like HIV-1, utilizes CCR5), driving its frequency upward in ancestral Caucasian populations.
