Article
Propionic acidemia and sensorineural hearing loss – a molecular genetic analysis
Search Medline for
Authors
Published: | September 7, 2006 |
---|
Outline
Text
Current Knowledge: The cumulative incidence of metabolic disease is around 1 in 100. One of these, propionic acidemia, is caused by a gene defect leading to a malfunction of the enzyme propionyl-CoA-carboxylase (PCC). This leads to a pathologic accumulation of propionic acid. Many mutations have been found at the molecular genetic level over the past 20 years and their consequences for the limitation of enzyme activity of PCC in propionic acidemia discussed.
Scientific Question and Aims of the Study: The increased incidence of deafness in patients with propionic acidemia suggests that mutations primarily responsible for this disease could also be the underlying cause for a genetic form of deafness.
Methods and Results: A standard pure tone audiogram and pedigree were set up. DNA extraction was obtained from either blood from the antecubital vein (30ml EDTA) or a buccal smear from 4 patients and 16 relatives. In one family a few relatives displayed two mutations. The mutation p.I450V (previously described in 1999) of the PCCA subunit showed no pathological influence on the enzyme activity of one female heterozygous patient.
Conclusions: The mutation of the PCCB subunit p.R113X has not yet been described in the literature and could be associated with deafness in the described patient.
Key Words: Propionic acidemia – sensorineural hearing loss – molecular genetics