ABSTRACT
Abnormal CAG expansions in the IT-15 gene are associated with Huntington disease (HD). In the diagnostic setting it is necessary to define the limits of the CAG size ranges on normal and HD-associated chromosomes. Most large analyses that defined the limits of the normal and pathological size ranges employed PCR assays, which included the CAG repeats and a CCG repeat tract that was thought to be invariant. Many of these experiments found an overlap between the normal and disease size ranges. Subsequent findings that the CCG repeats vary by 8 trinucleotide lengths suggested that the limits of the normal and disease size ranges should be reevaluated with assays that exclude the CCG polymorphism. Since patients with between 30 and 40 repeats are rare, a consortium was assembled to collect such individuals. All 178 samples were reanalyzed in Cambridge by using assays specific for the CAG repeats. We have optimized methods for reliable sizing of CAG repeats and show cases that demonstrate the dangers of using PCR assays that include both the CAG and CCG polymorphisms. Seven HD patients had 36 repeats, which confirms that this allele is associated with disease. Individuals without apparent symptoms or signs of HD were found at 36 repeats (aged 74, 78, 79, and 87 years), 37 repeats (aged 69 years), 38 repeats (aged 69 and 90 years), and 39 repeats (aged 67, 90, and 95 years). The detailed case histories of an exceptional case from this series will be presented: a 95-year-old man with 39 repeats who did not have classical features of HD. The apparently healthy survival into old age of some individuals with 36-39 repeats suggests that the HD mutation may not always be fully penetrant.
Subject(s)
Huntington Disease/genetics , Minisatellite Repeats , Phenotype , Trinucleotide Repeats , Adult , Aged , Aged, 80 and over , Female , Humans , Huntington Disease/diagnosis , Male , Middle Aged , Mutation , Polymerase Chain Reaction , Reference ValuesABSTRACT
Symptoms of schizophrenia may be encountered in Huntington's disease (HD) but usually when the full clinical syndrome is apparent; prechoreic psychosis is relatively uncommon. We describe a family where all four members affected with HD presented first with a severe psychiatric syndrome, which in three cases was schizophreniform in nature. Two other living members with no current signs of motor disorder have received psychiatric treatment, one for schizophrenia. Concurrence of psychosis and Huntington's disease in this family is unlikely to have occurred by chance, suggesting that there is some feature in this family which gives rise to the psychotic presentation. Families such as this may contribute to the investigation of genetic factors associated with psychiatric illnesses.
Subject(s)
Huntington Disease/psychology , Neurocognitive Disorders/genetics , Psychotic Disorders/genetics , Adult , Age of Onset , Dementia/epidemiology , Dementia/genetics , Depression/diagnosis , Depression/genetics , Female , Humans , Huntington Disease/diagnosis , Huntington Disease/epidemiology , Huntington Disease/genetics , Male , Minisatellite Repeats , Neurocognitive Disorders/diagnosis , Neurocognitive Disorders/epidemiology , Pedigree , Psychotic Disorders/diagnosis , Psychotic Disorders/epidemiologyABSTRACT
A novel NcoI polymorphism has been detected in the 3' untranslated region of the creatinine kinase (CKM) gene. The addition NcoI restriction site creates a fifth haplotype for the NcoI and TaqI restriction fragments length polymorphisms at this locus, and segregates with the myotonic dystrophy gene in 3 generations of an affected family.
