|Huntington's disease is an autosomal dominant neurodegenerative
disorder caused by the expansion of a (CAG)n repeat in the IT15 gene.
Three per cent of cases are sporadic
and in those in which family studies have been performed, the origin of the mutation was always paternal.
sporadic case of Huntington's disease is presented in which a premutated maternal allele of 37 CAG repeats was transmitted
to the proband (43 CAG repeats). Molecular analysis of the IT15 gene is extremely important in sporadic cases of Huntington's
disease, providing correct diagnosis of the disorder and facilitating
genetic counselling to the family members.
Source: Journal of Neurology, Neurosurgery, and Psychiatry, 1997, Vol 62, 535-537 Maternal transmission in sporadic Huntington's disease A Sanchez, M Mila, S Castellvi-Bel, M Rosich,
D Jimenez, C Badenas
and X Estivill Genetics Service, Hospital Clinic, Barcelona, Spain.
We describe a new approach for analysis of the epidemiology of progressive genetic disorders
that quantifies the rate of progression of the disease in the population
by measuring the mutational flow.
The framework is applied to Huntington disease (HD), a dominant neurological
caused by the expansion of a CAG-trinucleotide sequence to >35 repeats. The disease is 100% penetrant in individuals with
> or = 42 repeats.
Measurement of the flow from disease alleles provides a minimum estimate of the flow in
the whole population and implies that the
new mutation rate for HD in each generation is > or = 10% of currently
known cases (95% confidence limits 6%-14%).
Analysis of the pattern of flow demonstrates systematic underascertainment for repeat lengths <44. Ascertainment falls to <50% for individuals with 40 repeats and to <5% for individuals with 36-38 repeats.
Clinicians should not assume that HD is rare outside known pedigrees or
that most cases have onset at age <50 years.
In February 2991 , Dr. Michael Hayden and colleagues estimated a mutation
rate of ten percent.
Measurement of mutational flow
implies both a high new-mutation rate for Huntington disease and substantial underascertainment of late-onset cases.
D, Almqvist EW, Brinkmann RR, Iwasa Y, Hayden MR.Department of Biology, Faculty of Science, Kyushu University, Japan.