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A novel point mutation (Pro84 ← Ser) of the low density lipoprotein receptor gene in a family with moderate hypercholesterolemia
Author(s) -
Vuorio Alpo F.,
Turtola Hannu,
Kontula Kimmo
Publication year - 1997
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1997.tb02451.x
Subject(s) - familial hypercholesterolemia , ldl receptor , point mutation , proband , single strand conformation polymorphism , genetics , mutation , biology , restriction fragment length polymorphism , exon , genotype , lipoprotein , gene , microbiology and biotechnology , endocrinology , cholesterol
To obtain insight into the possibility that genetic variation of the structure of the low density lipoprotein (LDL) receptor protein could result in subtle changes of serum cholesterol levels, we used single‐strand conformation polymorphism (SSCP) to screen all 18 exons of the LDL receptor gene in a panel of subjects with moderate hypercholesterolemia. One novel mutation, replacing C to T at nucleotide 313 and predicted to cause a substitution of serine for proline at codon 84, was identified in a single proband. A convenient PCR assay based on the use of primer‐introduced restriction fragment length polymorphism was set up for the detection of this mutation. However, the pathophysiologic significance of the Pro84 → Ser replacement remains to be clarified, as serum LDL cholesterol levels were not significantly higher in mutation carriers vs. non‐carriers in the affected family, and no other proband was identified, on screening of DNA samples from 350 Finns. The Pro84 → Ser mutation represents the second single‐amino acid change of the LDL receptor protein so far reported which is not associated with the clinical phenotype of familial hypercholesterolemia.