Pedigree, telomere length, and BM histology. (A) Pedigree of proband (III-3). Individuals II-2 and II-3 are suspected mutation carriers. Slashed symbols indicate deceased (d.) individuals. Neither the proband, her sister, or affected nephew showed abnormal pigmentation of the skin, nail dystrophy, or oral leukoplakia, nor was there evidence of pulmonary or immunologic problems, growth retardation, developmental delay, or microcephaly. During cholecystectomy, an enlarged liver was noticed in III-2; however, this finding was not further evaluated after surgery. (B) Blood leukocyte telomere length (in kilobases) as a function of age. Mutation carriers have very short telomeres in peripheral blood leukocytes. The curve marks the 50th percentile of telomere length for control subjects derived from 298 healthy National Institutes of Health blood bank donors. A sample's telomere length was expressed as a telomere to single-copy gene (T/S) ratio, which was converted to kilobases. BM biopsy showed profound hypocellularity in the proband (III-3; C) and hypocellular BM and eosinophilic ground substance in her sister (III-2; D).