Academic Journal
Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis
| العنوان: | Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis |
|---|---|
| المؤلفون: | Papazachariou, L, Papagregoriou, G, Hadjipanagi, D, Demosthenous, P, Voskarides, K, Koutsofti, C, Stylianou, K, Ioannou, P, Xydakis, D, Tzanakis, I, Papadaki, A, Kallivretakis, N, Nikolakakis, N, Perysinaki, G, Gale, DP, Diamantopoulos, A, Goudas, P, Goumenos, D, Soloukides, A, Boletis, I, Melexopoulou, C, Georgaki, E, Frysira, E, Komianou, F, Grekas, D, Paliouras, C, Alivanis, P, Vergoulas, G, Pierides, A, Daphnis, E, Deltas, C |
| المصدر: | Clinical Genetics , 92 (5) (2017) |
| سنة النشر: | 2017 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | Alport Syndrome, COL4A3/COL4A4/COL4A5, end stage renal disease (ESRD), familial microscopic hematuria, focal segmental glomerulosclerosis (FSGS), later-onset Alport-related nephropathy (LOAN), next generation sequencing, thin basement membrane nephropathy (TBMN) |
| الوصف: | Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using Next Generation Sequencing (NGS) for five genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, nine of them novel. In five families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, eight (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-yrs, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | https://discovery.ucl.ac.uk/id/eprint/1560088/1/2017%20Papazachariou%20et%20al%20Clinical%20Genet%20accepted%202017.pdf; https://discovery.ucl.ac.uk/id/eprint/1560088/ |
| الاتاحة: | https://discovery.ucl.ac.uk/id/eprint/1560088/1/2017%20Papazachariou%20et%20al%20Clinical%20Genet%20accepted%202017.pdf https://discovery.ucl.ac.uk/id/eprint/1560088/ |
| Rights: | open |
| رقم الانضمام: | edsbas.15ABB347 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |