A novel homozygous RIPK4 variant in a family with severe Bartsocas-Papas syndrome
| Autor: | Evren Gumus, Zafer Yüksel, Gokhan Yildiz, Tuba Dinçer, Ersan Kalay, İdris Er, Bayram Toraman |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Ectodermal dysplasia Knee Joint Cleft Lip 030105 genetics & heredity Biology Protein Serine-Threonine Kinases urologic and male genital diseases Fingers 03 medical and health sciences Pregnancy Genetics medicine Coding region Humans Abnormalities Multiple Exome Genetic Predisposition to Disease Knee Syndactyly Eye Abnormalities Kinase activity Phosphorylation Transversion Gene Genetics (clinical) Homozygote Infant Newborn medicine.disease Phenotype 3. Good health Cleft Palate 030104 developmental biology Protein kinase domain Urogenital Abnormalities Aborted Fetus Mutation Skin Abnormalities Female hormones hormone substitutes and hormone antagonists Lower Extremity Deformities Congenital |
| Zdroj: | American journal of medical genetics. Part AREFERENCES. 185(6) |
| ISSN: | 1552-4833 |
| Popis: | Bartsocas-Papas syndrome (BPS) is a rare autosomal recessive disorder characterized by popliteal pterygia, syndactyly, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and genital malformations. Most of the BPS cases reported to date are fatal either in the prenatal or neonatal period. Causative genetic defects of BPS were mapped on the RIPK4 gene encoding receptor-interacting serine/threonine kinase 4, which is critical for epidermal differentiation and development. RIPK4 variants are associated with a wide range of clinical features ranging from milder ectodermal dysplasia to severe BPS. Here, we evaluated a consanguineous Turkish family, who had two pregnancies with severe multiple malformations compatible with BPS phenotype. In order to identify the underlying genetic defect, direct sequencing of the coding region and exon-intron boundaries of RIPK4 was carried out. A homozygous transversion (c.481G>C) that leads to the substitution of a conserved aspartic acid to histidine (p.Asp161His) in the kinase domain of the protein was detected. Pathogenicity predictions, molecular modeling, and cell-based functional assays showed that Asp161 residue is required for the kinase activity of the protein, which indicates that the identified variant is responsible for the severe BPS phenotype in the family. |
| Databáze: | OpenAIRE |
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