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Screening of EDA1 Gene in X-Linked Anhidrotic Ectodermal Dysplasia Using DHPLC: Identification of 14 Novel Mutations in Italian Patients
- Source :
- Genetic Testing. 12:437-442
- Publication Year :
- 2008
- Publisher :
- Mary Ann Liebert Inc, 2008.
-
Abstract
- Mutations within EDA1 gene, which encodes for the ectodysplasin, cause X-linked anhidrotic ectodermal dysplasia. In this study, 23 Italian patients with anhidrotic ectodermal dysplasia were analyzed for mutations in EDA1 gene. We set up a rapid protocol through denaturing high-performance liquid chromatography, followed by sequencing, that allowed the characterization of 18 mutations, 14 novel and 4 recurrent: 8 missense mutations (p.L51Q, p.H54R, p.R156H twice, p.C332F, p.D316H, p.T378M, and p.A349T), 3 in-frame deletions (p.G82_P84del, p.A179_P191del, and p.L354del), 1 gross deletion (p.G168_G265del, identified through direct sequencing and PCR), 4 altered splicing (c.949-13T > C, c.741 + 1G/T, c.793 + 4A > T, and c.924 + 1G/T), 1 nonsense (p.Y3X), and 1 synonymous mutation (c.741G > A). Moreover, structural analysis of three missense mutations shows that alteration of the electrostatic surface of the protein (p.D316N), the break of intermonomer interactions (p.A349T) and destabilization of the single monomer structure (p.T378M), may irreversibly invalidate the EDA-A1 binding properties. Our data confirm and extend the large spectrum of EDA1 mutations and provide a rapid and efficient molecular protocol for testing EDA1 mutations in EDA patients.
- Subjects :
- Models, Molecular
Silent mutation
Ectodermal dysplasia
media_common.quotation_subject
Static Electricity
Nonsense
Mutation, Missense
Biology
Models
Hydrophobic and Hydrophilic Interactions
Humans
Chromatography, High Pressure Liquid
Italy
Gene Deletion
Codon, Nonsense
Genetic Testing
Ectodysplasins
Alternative Splicing
Mutation
Hydrogen Bonding
Ectodermal Dysplasia 1, Anhidrotic
medicine
Missense mutation
Codon
Gene
Genetics (clinical)
media_common
Genetics
Chromatography
Direct sequencing
Binding properties
Molecular
medicine.disease
Molecular biology
Settore MED/03 - Genetica Medica
Anhidrotic
High Pressure Liquid
Ectodermal Dysplasia 1
RNA splicing
Missense
Subjects
Details
- ISSN :
- 15577473 and 10906576
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Genetic Testing
- Accession number :
- edsair.doi.dedup.....4767b6462819bbd46b503c9b77b9209d