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Mucolipidosis II: a single causal mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTAB) in a French Canadian founder population
- Source :
- Clinical genetics. 73(3)
- Publication Year :
- 2008
-
Abstract
- Mucolipidosis (ML) II (I-cell disease) is a lysosomal storage disorder caused by a deficiency of UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. MLII is an autosomal recessive disease with a carrier rate estimated at 1/39 in Saguenay-Lac-Saint-Jean (SLSJ) (Quebec, Canada), which is the highest frequency documented worldwide. To identify the causing mutation, we sequenced GNPTAB exons in 27 parents of 16 MLII-deceased children from the SLSJ region as obligatory and potential carriers. We also performed a genealogical reconstruction for each parent to evaluate consanguinity levels and genetic contribution of ancestors. Our goal was to identify which parameters could explain the high MLII frequency observed in the SLSJ population. A single mutation (c.3503_3504delTC) was found in all obligatory carriers. In addition, 11 apparent polymorphisms were identified. The mutation was not detected in genomic DNA of 50 unrelated controls. Genealogical data show six founders (three couples) with a higher probability of having introduced the mutation in the population. The frequency of the mutation was increased as a consequence of this founder effect and of the resulting population structure. We suggest that c.3503_3504delTC is the allele causing MLII in the SLSJ population, and its high carrier rate is most likely explained by a founder effect.
- Subjects :
- Canada
Population
DNA Mutational Analysis
Transferases (Other Substituted Phosphate Groups)
Consanguinity
Biology
GNPTG
White People
Mucolipidoses
Genetics
medicine
Humans
Allele
education
Genetics (clinical)
education.field_of_study
Geography
Mucolipidosis
medicine.disease
Founder Effect
Case-Control Studies
Mutation (genetic algorithm)
Mutation
I-cell disease
Founder effect
Genealogy and Heraldry
Subjects
Details
- ISSN :
- 13990004
- Volume :
- 73
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Clinical genetics
- Accession number :
- edsair.doi.dedup.....db22db60f9ccc25f6661af735ee826a3