Complete loss of function of HBS1L results in a unique phenotype without hematologic abnormalities. (A) Sanger sequencing confirms the presence of compound heterozygosity for 2 loss-of-function mutations in HBS1L inherited from the father and mother, respectively. (B) Western blotting demonstrates the absence of HBS1L protein in 2 samples of fibroblasts from the proband, whereas it is present in 2 control samples. A tubulin β (TUBB1) loading control is present in similar amounts in all 4 samples. (C) A representative image of a blood smear shown at 100× shows normal red cell morphology without any other notable abnormalities, consistent with what is seen from examination of hundreds of similar fields. (D) Hemoglobin high-performance liquid chromatography analysis shows a normal distribution of hemoglobin subtypes in the patient.