Inherited ichthyoses: molecular causes of the disease in Czech patients
Abstract Inherited ichthyoses belong to a large and heterogeneous group of mendelian disorders of cornification, and can be distinguished by the quality and distribution of scaling and hyperkeratosis, by other dermatologic and extracutaneous involvement, and by inheritance. We present the genetic an...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-05-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-019-1076-7 |
| _version_ | 1819104024020910080 |
|---|---|
| author | Romana Borská Blanka Pinková Kamila Réblová Hana Bučková Lenka Kopečková Jitka Němečková Alena Puchmajerová Marcela Malíková Markéta Hermanová Lenka Fajkusová |
| author_facet | Romana Borská Blanka Pinková Kamila Réblová Hana Bučková Lenka Kopečková Jitka Němečková Alena Puchmajerová Marcela Malíková Markéta Hermanová Lenka Fajkusová |
| author_sort | Romana Borská |
| collection | DOAJ |
| description | Abstract Inherited ichthyoses belong to a large and heterogeneous group of mendelian disorders of cornification, and can be distinguished by the quality and distribution of scaling and hyperkeratosis, by other dermatologic and extracutaneous involvement, and by inheritance. We present the genetic analysis results of probands with X-linked ichthyosis, autosomal recessive congenital ichthyosis, keratinopathic ichthyosis, and a patient with Netherton syndrome. Genetic diagnostics was complemented by in silico missense variant analysis based on 3D protein structures and commonly used prediction programs to compare the yields of these two approaches to each other. This analysis revealed various structural defects in proteins coded by mutated genes while no defects were associated with known polymorphisms. Two patients with pathogenic variants in the ABCA12 gene have a premature termination codon mutation on one allele and a silent variant on the second. The silent variants c.69G > A and c.4977G > A are localised in the last nucleotide of exon 1 and exon 32, respectively, and probably affect mRNA splicing. The phenotype of both patients is very severe, including a picture harlequin foetus after birth; later (at 3 and 6 years of age, respectively) ectropin, eclabion, generalised large polygonal scaling and erythema. |
| first_indexed | 2024-12-22T01:59:46Z |
| format | Article |
| id | doaj.art-43bc9ac616384e6fadfac80169ee5993 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-22T01:59:46Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-43bc9ac616384e6fadfac80169ee59932022-12-21T18:42:41ZengBMCOrphanet Journal of Rare Diseases1750-11722019-05-011411510.1186/s13023-019-1076-7Inherited ichthyoses: molecular causes of the disease in Czech patientsRomana Borská0Blanka Pinková1Kamila Réblová2Hana Bučková3Lenka Kopečková4Jitka Němečková5Alena Puchmajerová6Marcela Malíková7Markéta Hermanová8Lenka Fajkusová9Centre of Molecular Biology and Gene Therapy, University Hospital Brno and Masaryk UniversityDepartment of Pediatric Dermatology, Pediatric Clinic, University Hospital Brno and Masaryk UniversityCentral European Institute of Technology, Masaryk UniversityDepartment of Pediatric Dermatology, Pediatric Clinic, University Hospital Brno and Masaryk UniversityCentre of Molecular Biology and Gene Therapy, University Hospital Brno and Masaryk UniversityDepartment of Medical Genetics, University Hospital BrnoInstitute of Biology and Medical Genetics, University Hospital MotolInstitute of Biology and Medical Genetics, University Hospital MotolFirst Department of Pathological Anatomy, Faculty of Medicine, Masaryk University and St. Anne’s University HospitalCentre of Molecular Biology and Gene Therapy, University Hospital Brno and Masaryk UniversityAbstract Inherited ichthyoses belong to a large and heterogeneous group of mendelian disorders of cornification, and can be distinguished by the quality and distribution of scaling and hyperkeratosis, by other dermatologic and extracutaneous involvement, and by inheritance. We present the genetic analysis results of probands with X-linked ichthyosis, autosomal recessive congenital ichthyosis, keratinopathic ichthyosis, and a patient with Netherton syndrome. Genetic diagnostics was complemented by in silico missense variant analysis based on 3D protein structures and commonly used prediction programs to compare the yields of these two approaches to each other. This analysis revealed various structural defects in proteins coded by mutated genes while no defects were associated with known polymorphisms. Two patients with pathogenic variants in the ABCA12 gene have a premature termination codon mutation on one allele and a silent variant on the second. The silent variants c.69G > A and c.4977G > A are localised in the last nucleotide of exon 1 and exon 32, respectively, and probably affect mRNA splicing. The phenotype of both patients is very severe, including a picture harlequin foetus after birth; later (at 3 and 6 years of age, respectively) ectropin, eclabion, generalised large polygonal scaling and erythema.http://link.springer.com/article/10.1186/s13023-019-1076-7Autosomal recessive congenital ichthyosisKeratinopathic ichthyosisIn silico analysis3D protein structure |
| spellingShingle | Romana Borská Blanka Pinková Kamila Réblová Hana Bučková Lenka Kopečková Jitka Němečková Alena Puchmajerová Marcela Malíková Markéta Hermanová Lenka Fajkusová Inherited ichthyoses: molecular causes of the disease in Czech patients Orphanet Journal of Rare Diseases Autosomal recessive congenital ichthyosis Keratinopathic ichthyosis In silico analysis 3D protein structure |
| title | Inherited ichthyoses: molecular causes of the disease in Czech patients |
| title_full | Inherited ichthyoses: molecular causes of the disease in Czech patients |
| title_fullStr | Inherited ichthyoses: molecular causes of the disease in Czech patients |
| title_full_unstemmed | Inherited ichthyoses: molecular causes of the disease in Czech patients |
| title_short | Inherited ichthyoses: molecular causes of the disease in Czech patients |
| title_sort | inherited ichthyoses molecular causes of the disease in czech patients |
| topic | Autosomal recessive congenital ichthyosis Keratinopathic ichthyosis In silico analysis 3D protein structure |
| url | http://link.springer.com/article/10.1186/s13023-019-1076-7 |
| work_keys_str_mv | AT romanaborska inheritedichthyosesmolecularcausesofthediseaseinczechpatients AT blankapinkova inheritedichthyosesmolecularcausesofthediseaseinczechpatients AT kamilareblova inheritedichthyosesmolecularcausesofthediseaseinczechpatients AT hanabuckova inheritedichthyosesmolecularcausesofthediseaseinczechpatients AT lenkakopeckova inheritedichthyosesmolecularcausesofthediseaseinczechpatients AT jitkanemeckova inheritedichthyosesmolecularcausesofthediseaseinczechpatients AT alenapuchmajerova inheritedichthyosesmolecularcausesofthediseaseinczechpatients AT marcelamalikova inheritedichthyosesmolecularcausesofthediseaseinczechpatients AT marketahermanova inheritedichthyosesmolecularcausesofthediseaseinczechpatients AT lenkafajkusova inheritedichthyosesmolecularcausesofthediseaseinczechpatients |