Genetics
CETP D442G mutation is found in two families with Lowe syndrome and elevated HDL cholesterol (Acta Paediatr 1997)
Original title: Two families of Lowe oculocerebrorenal syndrome with elevated serum HDL cholesterol levels and CETP gene mutation
Oculocerebrorenal syndrome of Lowe, an X-linked disorder marked by renal tubular dysfunction, congenital cataracts, and cognitive impairment, has been reported to frequently include hypercholesterolemia driven by elevated HDL cholesterol. Examining three Lowe syndrome children from two unrelated families, this study confirmed high serum HDL-C in all three patients and also found it in 5 of 7 unaffected family members. CETP gene analysis, screening for variants already known to raise serum HDL-C, identified the D442G mutation in exon 15 in 5 of 10 family members, comprising 1 of 3 patients and 4 of 7 healthy relatives, with no intron 14 splice defect detected, suggesting D442G contributes to the elevated HDL-C seen in these two families alongside their underlying Lowe syndrome.
Original abstract
The ocuolocerebrorenal syndrome of Lowe (OCRL) is an X-linked recessive disorder which is characterized by renal tubular dysfunction, congenital cataracts, and cognitive impairment. In a review article by Charnas et al. (N Engl J Med 1991; 324: 1318-25), hypercholesterolemia, due to elevated high-density lipoprotein cholesterol (HDL-C) levels, was described as being highly prevalent in OCRL patients. This report prompted us to examine three OCRL children in two unrelated families and we confirmed the high prevalence of high serum HDL-C levels in the patients (3/3). In addition, we found that their normal family members also had high serum HDL-C levels (5/7). Analysis of cholesteryl ester transfer protein (CETP) genes, which are now recognized as one of factors increasing serum HDLC levels, revealed the D442G mutation in exon 15 in 5 of 10 family members (1/3 of OCRL patients and 4/7 healthy family members), and no mutation of intron 14 G(+1)-to-A. The detected D442G mutation may be one of the causes in our two OCRL families; however, further studies, based on larger numbers of subjects, are needed to confirm these findings.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.