Family pedigrees. (A) The arrow indicates the proband. Family A and Family B: Asterisks indicate individuals evaluated with targeted gene capture panel/high-throughput sequencing. The variant allele (295C>T; R99W) is indicated with V1, and reference alleles are indicated with an N. Family C: Asterisk indicates individual evaluated with whole-exome sequencing. The variant allele (469C>T; R157X) is indicated with V2, and reference alleles are indicated with an N. (B) Serum THPO levels in affected individuals. Serum THPO concentrations (picograms per milliliter) are given for the affected child along with the testing laboratory’s control ranges. (C) THPO protein domains. The signal peptide (amino acid residues 1-21) is shaded in light red. The positions of the THPO mutations are indicated on the structure. (D) THPO amino acid conservation across vertebrate species. Bold font indicates the arginine residue at position 99 of the human THPO sequence. Twenty–amino acid residues flanking position 99 are shown (NCBI RefSeq). EPO, erythropoietin; N/A, not applicable.
