Related Experiment Videos
Mutations in MKKS cause Bardet-Biedl syndrome
A M Slavotinek1, E M Stone, K Mykytyn
1Genetic Diseases Research Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Nature Genetics
|September 6, 2000
Summary
McKusick-Kaufma syndrome (MKS) gene mutations were identified in Bardet-Biedl syndrome (BBS) patients, linking MKS to BBS. This discovery helps understand the genetic basis of BBS and related disorders.
Area of Science:
- Genetics and Molecular Biology
- Human Disease Genetics
- Clinical Genetics
Background:
- Bardet-Biedl syndrome (BBS) is a complex autosomal recessive disorder with genetic heterogeneity, where causative genes remain largely unidentified.
- Approximately 10% of BBS cases are not linked to previously mapped loci, indicating the involvement of undiscovered genes.
- McKusick-Kaufma syndrome (MKS) is another autosomal recessive disorder characterized by hydrometrocolpos, postaxial polydactyly, and congenital heart disease.
Purpose of the Study:
- To investigate the genetic underpinnings of Bardet-Biedl syndrome in families unsuitable for traditional linkage analysis.
- To identify novel genes responsible for BBS phenotypes, particularly in cases not assigned to known BBS loci.
- To explore the potential genetic overlap between Bardet-Biedl syndrome and McKusick-Kaufma syndrome.
Main Methods:
- Ascertainment of 34 unrelated probands with classic BBS features, including retinitis pigmentosa, obesity, and polydactyly.
- Genetic analysis of probands and families, including mutation screening of the McKusick-Kaufma syndrome gene (MKKS).
- Allele sequencing, cloning, and genotyping to confirm mutation presence, zygosity, and chromosomal location (20p12).
Main Results:
- Mutations in the MKKS gene were identified in four probands with typical Bardet-Biedl syndrome.
- Identified mutations include a compound heterozygote with missense and nonsense mutations, and a homozygote with two deletions causing a frameshift.
- Affected individuals exhibited a spectrum of BBS features, including severe retinitis pigmentosa, obesity, mental retardation, and renal abnormalities.
Conclusions:
- The McKusick-Kaufma syndrome gene (MKKS) is implicated in a subset of Bardet-Biedl syndrome cases, expanding the known genetic causes of BBS.
- This finding highlights locus heterogeneity in BBS and suggests a potential genetic link between BBS and MKS.
- Identification of MKKS mutations provides new diagnostic avenues and insights into the molecular pathology of Bardet-Biedl syndrome.