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A novel insertion mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene underlies Grebe-type chondrodysplasia in a consanguineous Pakistani family.

Basit S, Naqvi SK, Wasif N, Ali G, Ansar M, Ahmad W - BMC Med. Genet. (2008)

Bottom Line: Genotyping results showed linkage of the family to CDMP1 locus.Sequence analysis of the CDMP1 gene identified a novel four bases insertion mutation (1114insGAGT) in exon 2 of the gene causing frameshift and premature termination of the polypeptide.Our findings extend the body of evidence that supports the importance of CDMP1 in the development of limbs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan. biochemistsulfi@yahoo.com

ABSTRACT

Background: Grebe-type chondrodysplasia (GCD) is a rare autosomal recessive syndrome characterized by severe acromesomelic limb shortness with non-functional knob like fingers resembling toes. Mutations in the cartilage-derived morphogenetic protein 1 (CDMP1) gene cause Grebe-type chondrodysplasia.

Methods: Genotyping of six members of a Pakistani family with Grebe-type chondrodysplasia, including two affected and four unaffected individuals, was carried out by using polymorphic microsatellite markers, which are closely linked to CDMP1 locus on chromosome 20q11.22. To screen for a mutation in CDMP1 gene, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected and unaffected individuals of the family and sequenced directly in an ABI Prism 310 automated DNA sequencer.

Results: Genotyping results showed linkage of the family to CDMP1 locus. Sequence analysis of the CDMP1 gene identified a novel four bases insertion mutation (1114insGAGT) in exon 2 of the gene causing frameshift and premature termination of the polypeptide.

Conclusion: We describe a 4 bp novel insertion mutation in CDMP1 gene in a Pakistani family with Grebe-type chondrodysplasia. Our findings extend the body of evidence that supports the importance of CDMP1 in the development of limbs.

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Related in: MedlinePlus

Sequence analysis of the CDMP1 gene mutation. DNA sequence of exon 2 of CDMP1 gene from (a) an affected individual (b) a heterozygous carrier and (c) a control individual. The bar in panel (a) represents the sequence that was inserted in the homozygous state in the affected individuals.
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Figure 4: Sequence analysis of the CDMP1 gene mutation. DNA sequence of exon 2 of CDMP1 gene from (a) an affected individual (b) a heterozygous carrier and (c) a control individual. The bar in panel (a) represents the sequence that was inserted in the homozygous state in the affected individuals.

Mentions: The entire coding portion and intron-exon boundaries of CDMP1 gene was sequenced in 6 individuals including two affected (IV-1 and IV-4) of the family. Sequence analysis of exon 2 of the CDMP1 gene from affected individual revealed a 4-bp insertion starting at nucleotide position 1114 (1114insGAGT) (Fig. 4a) resulting in immediate stop codon. This insertion was present in the heterozygous state in obligate carriers III-1 and III-2 (Fig. 4b). The mutation was not identified in normal individuals of the family (Fig. 4c). To ensure that the mutation does not represent a neutral polymorphism in this population, a panel of 40 unrelated unaffected ethnically matched control individuals was screened for the mutation and it was not identified outside the family.


A novel insertion mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene underlies Grebe-type chondrodysplasia in a consanguineous Pakistani family.

Basit S, Naqvi SK, Wasif N, Ali G, Ansar M, Ahmad W - BMC Med. Genet. (2008)

Sequence analysis of the CDMP1 gene mutation. DNA sequence of exon 2 of CDMP1 gene from (a) an affected individual (b) a heterozygous carrier and (c) a control individual. The bar in panel (a) represents the sequence that was inserted in the homozygous state in the affected individuals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2611973&req=5

Figure 4: Sequence analysis of the CDMP1 gene mutation. DNA sequence of exon 2 of CDMP1 gene from (a) an affected individual (b) a heterozygous carrier and (c) a control individual. The bar in panel (a) represents the sequence that was inserted in the homozygous state in the affected individuals.
Mentions: The entire coding portion and intron-exon boundaries of CDMP1 gene was sequenced in 6 individuals including two affected (IV-1 and IV-4) of the family. Sequence analysis of exon 2 of the CDMP1 gene from affected individual revealed a 4-bp insertion starting at nucleotide position 1114 (1114insGAGT) (Fig. 4a) resulting in immediate stop codon. This insertion was present in the heterozygous state in obligate carriers III-1 and III-2 (Fig. 4b). The mutation was not identified in normal individuals of the family (Fig. 4c). To ensure that the mutation does not represent a neutral polymorphism in this population, a panel of 40 unrelated unaffected ethnically matched control individuals was screened for the mutation and it was not identified outside the family.

Bottom Line: Genotyping results showed linkage of the family to CDMP1 locus.Sequence analysis of the CDMP1 gene identified a novel four bases insertion mutation (1114insGAGT) in exon 2 of the gene causing frameshift and premature termination of the polypeptide.Our findings extend the body of evidence that supports the importance of CDMP1 in the development of limbs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan. biochemistsulfi@yahoo.com

ABSTRACT

Background: Grebe-type chondrodysplasia (GCD) is a rare autosomal recessive syndrome characterized by severe acromesomelic limb shortness with non-functional knob like fingers resembling toes. Mutations in the cartilage-derived morphogenetic protein 1 (CDMP1) gene cause Grebe-type chondrodysplasia.

Methods: Genotyping of six members of a Pakistani family with Grebe-type chondrodysplasia, including two affected and four unaffected individuals, was carried out by using polymorphic microsatellite markers, which are closely linked to CDMP1 locus on chromosome 20q11.22. To screen for a mutation in CDMP1 gene, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected and unaffected individuals of the family and sequenced directly in an ABI Prism 310 automated DNA sequencer.

Results: Genotyping results showed linkage of the family to CDMP1 locus. Sequence analysis of the CDMP1 gene identified a novel four bases insertion mutation (1114insGAGT) in exon 2 of the gene causing frameshift and premature termination of the polypeptide.

Conclusion: We describe a 4 bp novel insertion mutation in CDMP1 gene in a Pakistani family with Grebe-type chondrodysplasia. Our findings extend the body of evidence that supports the importance of CDMP1 in the development of limbs.

Show MeSH
Related in: MedlinePlus