Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Mutational Analysis/methods , DNA-Binding Proteins , Germ-Line Mutation/genetics , Neoplasm Proteins/genetics , Proto-Oncogene Proteins/genetics , Adaptor Proteins, Signal Transducing , Baltic States/epidemiology , Carrier Proteins , Humans , MutL Protein Homolog 1 , MutS Homolog 2 Protein , Nuclear Proteins , Poland/epidemiologyABSTRACT
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.
Subject(s)
Muscle Spasticity/diagnosis , Optic Atrophies, Hereditary/diagnosis , Pantothenate Kinase-Associated Neurodegeneration/diagnosis , Adolescent , Adult , Child , Female , Humans , Male , Muscle Spasticity/etiology , Muscle Spasticity/genetics , Nuclear Family , Optic Atrophies, Hereditary/etiology , Optic Atrophies, Hereditary/genetics , Pantothenate Kinase-Associated Neurodegeneration/complications , Pantothenate Kinase-Associated Neurodegeneration/geneticsABSTRACT
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.
