195 - Spectrum of LDLR gene mutations, causing familial hypercholesterolemia (FH) in Greece: un update. (ID 1111)
Abstract
Background and Aims
Familial hypercholesterolemia (FH) is the most common genetic disorder of cholesterol metabolism, characterized by high levels of LDL-cholesterol. It is inherited as an autosomal dominant disorder mainly due to LDL receptor gene (LDLR) mutations. We determined the FH genetic basis and mapped the spectrum of LDLR mutations in children and adults of Greek origin.
Methods
The study included 50 patients, aged 7-56 years. Participants came from the Institute of Child Health's Metabolic Disorders Unit and the Outpatient Lipid Unit of 2nd Dpt of Pediatrics, Medical School, National & Kapodistrian University of Athens. Clinical diagnosis was based on the Dutch Lipid Clinic Network criteria. DNA Isolation, PCR amplification and LDLR gene sequencing were performed.
Results
No patients had xanthomas, 36% had a family history of early cardiovascular disease and 52% reported grade 1 familial dyslipidemia. The mean levels of total- and LDL-cholesterol were 294 and 220 mg/dl, respectively. 50% of the patients were diagnosed with FH-Genoa-Palermo, Greece-2, Greece-1, Reggio-Emilia, FH Algeria and San-Francisco mutations, while a 6% were compound heterozygotes with the mutations Cyprus-2, Greece-2 / San Francisco, Genoa / San-Francisco and FH-Puerto-Rico / Greece-2. For the first time, FH-Zampia, FH-Wallon, FH-Puerto-Rico and FH-Nuoro mutations were detected in individuals of Greek origin, while new variants, p.Gln384Ter, p.Cys222Ter and c.1646G> T (G528V) were observed.
Conclusions
The known LDLR mutations recorded in Greece covered only 50% of the subjects tested. The remaining 50% are new pathogenic variants, indicating the need for a more detailed classification of FH's genetic profile in Greece.
