A disease causing deletion of 29 base pairs in intron 15 in the MKS1 gene is highly associated with the campomelic variant of the Meckel-Gruber syndrome
| Autor: | Bernd Auber, K Schoner, R. Rauskolb, Helga Rehder, S Herold, G Simson, Peter Burfeind |
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| Rok vydání: | 2007 |
| Předmět: |
Central Nervous System
Male DNA Mutational Analysis Molecular Sequence Data Biology medicine.disease_cause 03 medical and health sciences Gene Frequency Genotype Genetics medicine Coding region Humans Abnormalities Multiple Genetic Testing Meckel syndrome Gene Genetics (clinical) 030304 developmental biology Meckel-Gruber Syndrome Sequence Deletion 0303 health sciences Mutation Base Sequence urogenital system 030305 genetics & heredity Intron Proteins Syndrome medicine.disease Introns 3. Good health Radiography Polydactyly Aborted Fetus Mutation testing Female |
| Zdroj: | Clinical genetics. 72(5) |
| ISSN: | 0009-9163 |
| Popis: | Meckel-Gruber syndrome (MKS) is an autosomal recessive disorder causing severe defects in the developing central nervous system and other organs. Recently, mutations in the MKS1 gene have been identified as disease causing in individuals of Finnish MKS families. The primary aim of the present study was to assess the frequency of the 'Finnish founder mutation' (29 bp IVS15-7_35) in the MKS1 gene in 20 aborted fetuses with a diagnosis of MKS. The secondary aim was to screen for novel mutations in the coding sequence of the MKS1 gene of MKS fetuses and to obtain genotype-phenotype correlations where possible. Furthermore, we evaluated the carrier rate of a deletion of 29 bp in intron 15 of the MKS1 gene in a German population. To identify and characterize mutations in the MKS1 gene, sequence analyses and quantitative real time polymerase chain reaction studies were performed. We could identify the same type of mutation, a deletion of 29 bp in intron 15 of the MKS1 gene, in 8 out of the 20 cases studied. Six out of the eight cases with such a mutation displayed the campomelic variant of MKS. The carrier frequency among 519 healthy German individuals was 1:260. This deletion in the MKS1 gene is highly associated with a distinct subtype of the MKS, namely the campomelic variant. In individuals of European origin suffering from the campomelic MKS variant, the described deletion is highly likely to be causative. Regarding the results of our study, the incidence of MKS in Germany can be estimated as 1:135,000. In families with a known mutation in the MKS1 gene, it is now possible to offer an early prenatal testing, for example with chorionic villus sampling and mutation analysis. |
| Databáze: | OpenAIRE |
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