Familial Hypercholesterolemia in an Azorean Family: A Novel Mutation in the Low-Density Lipoprotein Receptor Gene

Familial hypercholesterolemia (FH) is one of the most prevalent autosomal dominant inherited disorders. Mutations have been found in at least 3 genes: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). We report on an Azorean family with FH due to a novel mutation in the LDLR gene across three generations. The index-case was first seen at our endocrinology consultation at 12 years old, because of delayed growth and development. Laboratorial investigations revealed a complete failure of the anterior hypophysis due to a congenital malformation of the sella turcica. A total cholesterol of 313 mg/dL (90 - 190 mg/dL) and low-density lipoprotein cholesterol (LDL-C) of 262 mg/dL (<115 mg/dL) was found in routine blood tests. There was a paternal history of hypercholesterolemia, corneal arcus and myocardial infarction at an early age. Screening for mutations in LDLR gene was carried out. In the affected cases, an intronic heterozygous point mutation (c.818-3C > G) causing a premature termination of transcription (stop codon) was identified.