A novel missense mutation in cathepsin K (CTSK) gene in a consanguineous Pakistani family with pycnodysostosis.

Abstract

BACKGROUND:

Deficiency of cathepsin K (CTSK), a lysosomal cysteine protease, has been shown earlier as a cause of an autosomal recessive osteosclerotic skeletal dysplasia pycnodysostosis. The objective of the present study was to identify the potential sequence variants in CTSK gene in a large consanguineous Pakistani family with pycnodysostosis.

METHODS:

Genotyping of 4 affected and 6 unaffected members of the family was performed using polymorphic microsatellite markers linked to CTSK gene on chromosome 1q21. To screen for pathogenic mutation, exons and splice junctions of CTSK gene were polymerase chain reaction amplified from genomic DNA and sequenced directly in an automated DNA sequencer.

RESULTS:

Microsatellite analysis showed linkage of the family to CTSK gene on chromosome 1q21. Sequence analysis revealed a novel missense mutation c.728G>A (p.G243E) in exon 6 of the CTSK gene.

CONCLUSIONS:

A novel missense mutation was identified in CTSK gene in a Pakistani family with 5 individuals affected with autosomal recessive pycnodysostosis.

• Authors: Bushra Khan, Zahoor Ahmed, Wasim Ahmad
• Journal: Journal of investigative medicine : the official publication of the American Federation for Clinical Research (J Investig Med) Vol. 58 Issue 5 Pg. 720-4 (Jun 2010) ISSN: 1708-8267 [Electronic] England
• PMID: 20305575 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CTSK protein, human
• Cathepsin K

Topics

• Amino Acid Sequence
• Animals
• Cathepsin K (chemistry, genetics)
• Cattle
• Chromosome Disorders
• Consanguinity
• DNA Mutational Analysis
• Dogs
• Family Health
• Female
• Genes, Recessive (genetics)
• Genetic Linkage
• Genotype
• Humans
• Male
• Mice
• Microsatellite Repeats (genetics)
• Molecular Sequence Data
• Mutation, Missense
• Osteopetrosis (blood, genetics, pathology)
• Pakistan
• Pan troglodytes
• Rats
• Sequence Alignment
• Zebrafish