| Autor: |
Yingying Li, Liying Dai, Hong Xu, Jin Huang, Jinqiu Zhang, Zhenzhu Mei, Rui Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Molecular Genetics & Genomic Medicine, Vol 12, Iss 3, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2324-9269 |
| DOI: |
10.1002/mgg3.2399 |
| Popis: |
Abstract Background Nephronophthisis (NPHP) is a genetically heterogeneous disease that can lead to end‐stage renal disease (ESRD) in children. The TTC21B variant is associated with NPHP12 and mainly characterized by cystic kidney disease, skeletal malformation, liver fibrosis, and retinopathy. Affected patients range from children to adults. Some patients experience ESRD in infancy or early childhood, but clinical reports on neonatal patients are rare. We report a case of NPHP12 in a premature infant and analyze its genetic etiology. Methods Trio‐whole exome sequencing analysis was performed on the patient and her parents; bioinformatics software was used to predict and analyze the hazards of the variants. Sanger sequencing was performed to verify variants. We calculated the free energy between mutant IFT139 and the IFT121‐IFT122‐IFT43 complex structure using molecular dynamics (MD). Finally, the clinical and genetic characteristics of patients with hotspot variant Cys518Arg were reviewed. Results Genetic analysis revealed compound‐heterozyous TTC21B variants in the patient, c.497delA (p.Lys166fs*36) and c.1552T>C (p.Cys518Arg). Her father and mother had heterozygous c.497delA (p.Lys166fs*36) and heterozygous c.1552T>C (p.Cys518Arg), respectively. Cys518Arg represents a hotspot variant, and the MD calculation results show that this can reduce the structural stability of the IFT121‐IFT122‐IFT139‐IFT43 complex structure. A literature review showed that Cys518Arg might lead to the early occurrence of ESRD. Conclusions Compound‐heterozygous TTC21B variants underlie the phenotype in this patient. Thus, Cys518Arg may be a hotspot variant in the Chinese population. Genetic testing should be recommended for NPHP in neonates and early infants. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
