Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome
Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the <i>TP63</i> gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and diffe...
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MDPI AG
2023-06-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/6/1246 |
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| author | Anna Douka Lambros Goutzanis Dimitrios Vlachakis George P. Chrousos Christos Yapijakis |
| author_facet | Anna Douka Lambros Goutzanis Dimitrios Vlachakis George P. Chrousos Christos Yapijakis |
| author_sort | Anna Douka |
| collection | DOAJ |
| description | Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the <i>TP63</i> gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical AEC case of a four-year-old girl with extensive skin erosions and erythroderma of the scalp and the trunk, and to a lesser extent of the limbs, nail dystrophy on the fingers and toes, xerophthalmia, a high-arched palate, oligodontia, and hypohidrosis. Mutation analysis of the <i>TP63</i> gene detected a de novo missense mutation in exon 14 (c.1799G>T; p.Gly600Val). We discuss the phenotype–genotype correlation by presenting the clinical features of AEC in the patient, and the effect of the detected mutation in p63 structure and function using protein structural modeling, in view of similar cases in the literature. We performed a molecular modeling study in order to link the effect on the protein structure level of the missense mutation G600V. We noted that the introduction of the bulkier Valine residue in place of the slim Glycine residue caused a significantly altered 3D conformational arrangement of that protein region, pushing away the adjacent antiparallel α helix. We propose that the introduced locally altered structure of the G600V mutant p63 has a significant functional effect on specific protein–protein interactions, thus affecting the clinical phenotype. |
| first_indexed | 2024-03-11T02:25:18Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T02:25:18Z |
| publishDate | 2023-06-01 |
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| series | Genes |
| spelling | doaj.art-576a537f37fc488d9a590064bbe6ef822023-11-18T10:34:50ZengMDPI AGGenes2073-44252023-06-01146124610.3390/genes14061246Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting SyndromeAnna Douka0Lambros Goutzanis1Dimitrios Vlachakis2George P. Chrousos3Christos Yapijakis4Unit of Orofacial Genetics, 1st Department of Pediatrics, School of Medicine, National Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, 11527 Athens, GreeceDepartment of Oral and Maxillofacial Surgery, School of Dentistry, National Kapodistrian University of Athens, 11527 Athens, GreeceLaboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 11855 Athens, GreeceUniversity Research Institute for the Study of Genetic and Malignant Disorders in Childhood, Choremion Laboratory, “Aghia Sophia” Children’s Hospital, 11527 Athens, GreeceUnit of Orofacial Genetics, 1st Department of Pediatrics, School of Medicine, National Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, 11527 Athens, GreeceAnkyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the <i>TP63</i> gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical AEC case of a four-year-old girl with extensive skin erosions and erythroderma of the scalp and the trunk, and to a lesser extent of the limbs, nail dystrophy on the fingers and toes, xerophthalmia, a high-arched palate, oligodontia, and hypohidrosis. Mutation analysis of the <i>TP63</i> gene detected a de novo missense mutation in exon 14 (c.1799G>T; p.Gly600Val). We discuss the phenotype–genotype correlation by presenting the clinical features of AEC in the patient, and the effect of the detected mutation in p63 structure and function using protein structural modeling, in view of similar cases in the literature. We performed a molecular modeling study in order to link the effect on the protein structure level of the missense mutation G600V. We noted that the introduction of the bulkier Valine residue in place of the slim Glycine residue caused a significantly altered 3D conformational arrangement of that protein region, pushing away the adjacent antiparallel α helix. We propose that the introduced locally altered structure of the G600V mutant p63 has a significant functional effect on specific protein–protein interactions, thus affecting the clinical phenotype.https://www.mdpi.com/2073-4425/14/6/1246ectodermal dysplasiaankyloblepharonAEC syndrome<i>TP63</i> genecase reportp63 |
| spellingShingle | Anna Douka Lambros Goutzanis Dimitrios Vlachakis George P. Chrousos Christos Yapijakis Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome Genes ectodermal dysplasia ankyloblepharon AEC syndrome <i>TP63</i> gene case report p63 |
| title | Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome |
| title_full | Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome |
| title_fullStr | Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome |
| title_full_unstemmed | Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome |
| title_short | Molecular Modeling Analysis Provides Genotype–Phenotype Correlation Insights in a Patient with Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome |
| title_sort | molecular modeling analysis provides genotype phenotype correlation insights in a patient with ankyloblepharon ectodermal dysplasia clefting syndrome |
| topic | ectodermal dysplasia ankyloblepharon AEC syndrome <i>TP63</i> gene case report p63 |
| url | https://www.mdpi.com/2073-4425/14/6/1246 |
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