Thumbnail
Access Restriction
Open

Author DeStefano, A. L. ♦ Corwin, L. ♦ Farrer, L. A.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword BIOLOGY AND MEDICINE, BASIC STUDIES ♦ PATIENTS ♦ HEREDITARY DISEASES ♦ NERVOUS SYSTEM DISEASES ♦ AGE DEPENDENCE ♦ NUCLEOTIDES ♦ MUTATIONS ♦ GENES ♦ GENE MUTATIONS ♦ GENETIC MAPPING ♦ HUMAN CHROMOSOME 14 ♦ DOMINANT MUTATIONS ♦ STATISTICS
Abstract Machado-Joseph disease (MJD) is a late-onset, progressive, neurodegenerative disorder caused by the expansion of an unstable trinucleotide (CAG) repeat sequence in a novel gene (MJD1) on chromosome 14. Previous studies showed that age at onset is negatively correlated with the number of CAG repeat units, but only part of the variation in onset age is explained by CAG repeat length. Ages at onset and CAG repeat lengths of 136 MJD patients from 23 kindreds of Portuguese descent were analyzed, to determine whether familial factors independent of CAG repeat length modulate age at onset of MJD. Correlation among sibs for onset age adjusted for CAG repeat length was .43, which indicates that an environmental or genetic factor common to sibs influences onset age. Positive correlations were also observed for avuncular (r=.22) and first-cousin pairs (r=.28), which supports the hypothesis that a genetic factor is influencing age at onset. Commingling analysis of onset ages adjusted for CAG repeat length identified three distributions in this population of affected individuals. Further studies of a much larger sample are needed to determine whether these distributions represent the influence of a genetic or environmental factor. 43 refs., 2 figs., 3 tabs.
ISSN 00029297
Educational Use Research
Learning Resource Type Article
Publisher Date 1996-07-01
Publisher Place United States
Journal American Journal of Human Genetics
Volume Number 59
Issue Number 1


Open content in new tab

   Open content in new tab