Short stature and dysmorphic features in Asian Indian siblings with DAAM2‐associated steroid‐resistant nephrotic syndrome: Expansion of the phenotypic spectrum or a blended phenotype?

Abstract

AbstractVariants in more than 60 different genes, most of which code for podocyte‐related proteins, have been found to be associated with monogenic forms of nephrotic syndrome (NS). Biallelic variants in DAAM2, a member of the formin family, were recently identified to cause autosomal recessive (AR) NS type 24 in four unrelated families with steroid‐resistant nephrotic syndrome (SRNS). This case report represents only the fifth reported family of DAAM2‐associated NS and the first from India, with two sibs who presented with a complex phenotype characterized by steroid‐resistant nephrotic syndrome, short stature, dysmorphic facial features, deep‐set toenails, myopia, increased thickness of the calvarium of the skull, and sloping ribs. Both sibs were found to have a homozygous likely pathogenic nonsense variant c.196C>T (p.Arg66Ter; NM_001201427.2) in exon 3 of the DAAM2 gene through whole exome sequencing. The dysmorphic features could possibly be part of the DAAM2‐related phenotype which has hitherto not been reported or could represent a blended phenotype, with the extrarenal manifestations resulting from a yet to be identified coexisting genetic condition.