AUTHOR=Mastrangelo Antonio , Giani Marisa , Groppali Elena , Castorina Pierangela , Soldà Giulia , Robusto Michela , Fallerini Chiara , Bruttini Mirella , Renieri Alessandra , Montini Giovanni 

TITLE=X-Linked Alport Syndrome in Women: Genotype and Clinical Course in 24 Cases

JOURNAL=Frontiers in Medicine

VOLUME=7

YEAR=2020

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.580376

DOI=10.3389/fmed.2020.580376

ISSN=2296-858X

ABSTRACT=<p><bold>Objectives:</bold> X-linked Alport syndrome (XLAS) females are at risk of developing proteinuria and chronic kidney damage (CKD). The aim of this study is to evaluate the genotype-phenotype correlation in this rare population.</p><p><bold>Materials and Methods:</bold> This is a prospective, observational study of XLAS females, confirmed by a pathogenic mutation in <italic>COL4A5</italic> and renal ultrastructural evaluation. Proteinuria, renal function and extrarenal involvement were monitored during follow-up. Patients were divided in 2 groups, according to mutations in <italic>COL4A5</italic>: missense (Group 1) and non-missense variants (Group 2).</p><p><bold>Results:</bold> Twenty-four XLAS females, aged 10.6 ± 10.4 years at clinical onset (mean follow-up: 13.1 ± 12.6 years) were recruited between 2000 and 2017 at a single center. In group 1 there were 10 patients and in group 2, 14 (mean age at the end of follow-up: 24.9 ± 13.6 and 23.2 ± 13.8 years, respectively). One patient in Group 1 and 9 in Group 2 (<italic>p</italic> = 0.013) developed proteinuria during follow-up. Mean eGFR at last follow-up was lower in Group 2 (<italic>p</italic> = 0.027), where two patients developed CKD. No differences in hearing loss were documented among the two groups. Two patients in Group 2 carried one mutation in both <italic>COL4A5</italic> and <italic>COL4A3</italic> (digenic inheritance) and were proteinuric. In one family, the mother presented only hematuria while the daughter was proteinuric and presented a greater inactivation of the X chromosome carrying the wild-type allele.</p><p><bold>Conclusions:</bold> The appearance of proteinuria and CKD is more frequent in patients with severe variants. Carrying digenic inheritance and skewed XCI seem to be additional risk factors for proteinuria in XLAS females.</p>