Familial defective apolipoprotein (apo) B (FDB) and familial hypercholesterolaemia (FH) are the two common genetic conditions that cause hypercholesterolaemia. R3531C mutation of the APOB gene is a rare cause of FDB. Individuals with both FDB and FH are rare. A 51-year-old man with hypercholesterolaemia (11.4 mmol/L) and his family were studied. Low-density lipoprotein (LDL) receptor (LDLR) and APOB genes were analysed by direct sequencing. LDL of four subjects were studied in a fibroblast LDL receptor-binding displacement assay. We found a mutation of the LDLR gene (p.Y398X) in the proband and in four other family members: the p.R3531C APOB gene mutation was also found in the proband, his father and his children. The proband and his son were thus compound heterozygotes for both FH and FDB. Double heterozygotes did not show higher cholesterol levels compared to carriers of LDLR gene mutation alone. LDL from one of the carriers of the p.R3531C alone exhibited a binding ability, which was similar to a normal subject. This is the first report in Italy of the p.R3531C mutation, and our results show that this mutation has no effect in LDLR p.Y398X/APOB p.R3531C double heterozygotes.

Giammanco A., Spina R., Fayer F., Barbagallo C.M., Noto D., Cefalu A.B., et al. (2021). Lack of phenotypic additive effect of familial defective apolipoprotein B3531 in familial hypercholesterolaemia. INTERNAL MEDICINE JOURNAL, 51(4), 585-590 [10.1111/imj.15275].

Lack of phenotypic additive effect of familial defective apolipoprotein B3531 in familial hypercholesterolaemia

Giammanco A.
Writing – Original Draft Preparation
;
Spina R.
Writing – Original Draft Preparation
;
Fayer F.
Investigation
;
Barbagallo C. M.
Investigation
;
Noto D.
Formal Analysis
;
Cefalu A. B.
Conceptualization
;
Averna M
Conceptualization
2021

Abstract

Familial defective apolipoprotein (apo) B (FDB) and familial hypercholesterolaemia (FH) are the two common genetic conditions that cause hypercholesterolaemia. R3531C mutation of the APOB gene is a rare cause of FDB. Individuals with both FDB and FH are rare. A 51-year-old man with hypercholesterolaemia (11.4 mmol/L) and his family were studied. Low-density lipoprotein (LDL) receptor (LDLR) and APOB genes were analysed by direct sequencing. LDL of four subjects were studied in a fibroblast LDL receptor-binding displacement assay. We found a mutation of the LDLR gene (p.Y398X) in the proband and in four other family members: the p.R3531C APOB gene mutation was also found in the proband, his father and his children. The proband and his son were thus compound heterozygotes for both FH and FDB. Double heterozygotes did not show higher cholesterol levels compared to carriers of LDLR gene mutation alone. LDL from one of the carriers of the p.R3531C alone exhibited a binding ability, which was similar to a normal subject. This is the first report in Italy of the p.R3531C mutation, and our results show that this mutation has no effect in LDLR p.Y398X/APOB p.R3531C double heterozygotes.
Giammanco A., Spina R., Fayer F., Barbagallo C.M., Noto D., Cefalu A.B., et al. (2021). Lack of phenotypic additive effect of familial defective apolipoprotein B3531 in familial hypercholesterolaemia. INTERNAL MEDICINE JOURNAL, 51(4), 585-590 [10.1111/imj.15275].
File in questo prodotto:
File Dimensione Formato  
Internal Medicine Journal - 2021 - Giammanco - Lack of phenotypic additive effect of familial defective apolipoprotein.pdf

non disponibili

Descrizione: Articolo principale
Tipologia: Versione Editoriale
Dimensione 551.86 kB
Formato Adobe PDF
551.86 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/531463
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact