Albers_1981_Am.J.Hum.Genet_33_702

Lecithin-cholesterol acyltransferase (LCAT) mass was measured by radioimmunoassay in a large Sardinian kindred with LCAT deficiency. The frequency distribution of LCAT levels in the M-kindred demonstrated a trimodal distribution, one more corresponding to the normal controls and containing the normal relatives, a second mode completely separate from the controls and containing subjects with LCAT levels approximately one-half normal, and a third mode distinct from the other modes containing the two subjects with LCAT deficiency. Fifteen kindred members, including all six spouses, had enzyme levels of 4.92 +/- 0.49 microgram/ml (mean +/- SD), slightly lower but in the same range as controls (6.13 +/- 0.98; no. = 66). Twelve family members, including the two obligate heterozygotes, had enzyme levels of 2.68 +/- 0.32 microgram/ml, roughly one-half that of control levels. The LCAT-deficient subjects had enzyme levels of 0.30 and 0.37 microgram/ml, respectively. Segregation of the acyltransferase deficiency gene (LCATd) provided clear evidence of an autosomal recessive mode of inheritance of LCAT deficiency. Furthermore, the data strongly suggest that family members with half-normal enzyme levels are heterozygous carriers of the LCATd gene.