Mutational analysis of APOL1 in patients with Fechtner and Epstein syndromes: no evidence of a digenic etiology in MYH9-related disorders with renal disease

Maxine McGredy,¹ John A Martignetti,^1–3 Melanie Babcock<sup>1

1</sup>Departments of Genetics and Genomic Sciences, ²Pediatrics, ³Oncological Sciences, Mount Sinai School of Medicine, New York, NY, USA

Abstract: Mutations in MYH9 result in a group of clinically overlapping autosomal dominant macrothrombocytopenia syndromes, collectively termed the MYH9-related disorders (MYH9RD). Intriguingly, three of these disorders, Fechtner, Alport-like, and Epstein syndromes, are associated with the additional clinical phenotype of glomerulosclerosis. Recently, an abundance of studies have demonstrated that the APOL1 gene, contiguous to MYH9, is associated with a form of kidney disease in individuals of African ancestry. Given these findings related to kidney disease arising in mutations in two contiguous genes, this study aimed to determine whether APOL1 mutations could also be present in patients with Fechtner (FTNS) and Epstein (EPS) syndromes. This study used sequence analysis to investigate a discrete discovery set of FTNS patients, but did not identify second hit mutations in APOL1.

Keywords: APOL1, MYH9, Fechtner syndrome, Epstein syndrome