An 18 bps in-frame deletion mutation in RUNX2 gene is a population polymorphism rather than a pathogenic variant.
Eur J Med Genet
; 62(2): 124-128, 2019 Feb.
Article
in En
| MEDLINE
| ID: mdl-29960047
ABSTRACT
We recruited a family with an affected child exhibiting features of cleidocranial dysplasia with some phenotypic variations from reported cases. Whole exome sequencing data analysis identified an 18-bps heterozygous in-frame deletion variant (c.243-260delGGCGGCTGCGGCGGCGGC) in the RUNX2 gene. Sanger sequencing validated the presence of deletion in affected individual. Initially, we considered this variant as a causal mutation for the patient's phenotype based on previous report(s). However, further analysis of variant revealed that it is present in high frequency in variety of genome variation databases. Moreover, segregation analysis discovered the presence of variant in mother as well. Furthermore, screening of population matched control individuals revealed that the variant is present in apparently healthy individuals as well. Three-dimensional structures of the wild-type and mutant RUNX2 protein (p.Ala82_Ala87del) were analysed and it was found that both wild type and mutant protein show similar secondary structure pattern. Presence of RUNX2 deletion variant (c.243-260delGGCGGCTGCGGCGGCGGC) in control individuals, its high population frequency, benign effect on the overall protein structure lead to the argument that this variant is a population polymorphism and not a pathogenic mutation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
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Cleidocranial Dysplasia
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Gene Deletion
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Core Binding Factor Alpha 1 Subunit
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Gene Frequency
Type of study:
Prognostic_studies
Limits:
Adult
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Female
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Humans
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Infant
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Male
Language:
En
Journal:
Eur J Med Genet
Journal subject:
GENETICA MEDICA
Year:
2019
Document type:
Article
Affiliation country: