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. Author manuscript; available in PMC: 2022 May 1.
Published in final edited form as: Kidney Int. 2021 Jan 4;99(5):1102–1117. doi: 10.1016/j.kint.2020.12.022

Figure 1. Heterozygous nonsense mutation in MYO9A in a family with FSGS/proteinuria.

Figure 1.

A) novel heterozygous single-bp mutation that leads to a stop codon in exon 14 of MYO9A c.C2101T: p.R701X (p.Arg701*) in a patient with proteinuria and FSGS. Nucleotide sequence traces show the C>T mutation shared by proband, sister and mother (top, indicated by asterisk) and wild type sequence from the father (bottom), based on human MYO9A reference sequence NM_006901.4. B) Kidney biopsy from the proband shows focal segmental glomerular sclerosis, mild interstitial infiltrate (PAS stain). C) Family pedigree shows genotype-phenotype segregation: individuals with proteinuria/FSGS and MYO9Ap.R701X variant (solid symbols), wild type (empty symbol), (#) indicates unknown MYO9A genotype. D) Wild type MYO9A (NP_008832.2) protein domains: motor domain (grey) includes loop 2 (yellow) and calmodulin binding site (red), neck domain (blue), tail domain (pink) including RhoGAP domain (green); domain boundaries are indicated by amino acid residue number; predicted p.R701X MYO9A terminates within calmodulin binding site in loop 2, lacking the neck and tail domains, asterisks indicate the location of missense MYO9A VUS identified. E) Evolutionary conservation of amino acid residues altered by MYO9A missense mutations identified in FSGS patients: MYO9A altered residues p.D156 (p.Asp156) and p.E765 (p.Glu765) (red arrows) are highly conserved through phylogeny. Accession numbers: H. sapiens (NP_008832.2), M. musculus (NP_766606.2), R. norvegicus (NP_599162.1), G. gallus (XP_015134553.1), D. rerio (E7EZG2.1), X. tropicalis (XP_002934596.2) were used for MYO9A multiple sequence alignment with Clustal Omega-EMBL-EBI (https://www.ebi.ac.uk/Tools/msa/clustalo/).