𝔖 Bobbio Scriptorium
✦   LIBER   ✦

A new missense mutation (Cys297→Phe) of the low density lipoprotein receptor in Italian patients with familial hypercholesterolemia (FHTrieste)

✍ Scribed by N. Lelli; R. Garuti; P. Pedrazzi; M. Ghisellini; M. L. Simone; R. Tiozzo; L. Cattin; M. Valenti; M. Rolleri; S. Bertolini; C. Stefanutti; S. Calandra

Publisher
Springer
Year
1994
Tongue
English
Weight
561 KB
Volume
93
Category
Article
ISSN
0340-6717

No coin nor oath required. For personal study only.

✦ Synopsis

During a survey of the mutations of the low density lipoprotein receptor (LDL-R) gene in Italian patients with familial hypercholesterolemia (FH), we identified a novel point mutation, that creates a new EcoRI site at the 5" end of exon 7, in a heterozygous FH subject (FH-100). The sequence of a cDNA fragment encompassing exon 7 showed the presence of a G---~T transversion in codon 297; this created a new EcoRI site and produced a missense mutation, leading to a Cys297--~Phe substitution in repeat A of the epidermal growth factor (EGF) precursor homology domain of LDL-R. Since the substitution of Cys297 disrupts the intracellular transport of the LDL-R protein, as previously demonstrated by site-directed mutagenesis, we suggest that this mutation is the cause of FH in the FH-100 proband. We screened the DNA of 303 Italian FH patients by amplification of exon 7 from genomic DNA followed by digestion with EcoRI or by Southern blotting. Two individuals (FH-64 and FH-127) were found to be carriers of the Cys297--+Phe mutation. Restriction fragment length polymorphism analysis demonstrated that, in two kindreds (FH-64 and FH-100), the haplotype in linkage with the Cys297--~Phe mutation was the same, suggesting the presence of a common ancestor. The Cys297--->Phe mutation has been designated FHTriest e after the name of the city in Northern Italy from which probands FH-100 and FH-127 originate.

📜 SIMILAR VOLUMES

A missense mutation in the low density l
A missense mutation in the low density lipoprotein receptor gene causes familial hypercholesterolemia in Sephardic Jews
✍ Eran Leitersdorf; Ayeleth Reshef; Vardiella Meiner; Eldad J. Dann; Yitzhak Beige 📂 Article 📅 1993 🏛 Springer 🌐 English ⚖ 1000 KB

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low density lipoprotein (LDL) receptor gene. Here, we characterize an LDL receptor mutation that is associated with a distinct haplotype and that causes FH in the Jewish Sephardic population originating fr

Identification of a mutation in the low
Identification of a mutation in the low density lipoprotein receptor gene associated with recessive familial hypercholesterolemia in swine
✍ Hasler-Rapacz, Judith; Ellegren, Hans; Fridolfsson, Anna-Karin; Kirkpatrick, Bri 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 25 KB 👁 2 views

Elevated blood plasma cholesterol (hypercholesterolemia) is a major risk factor for coronary artery disease (CAD) in humans. Genetic dissection of polygenic lipid and lipoprotein disorders in swine, a key animal model for the study of familial hypercholesterolemia (FH) and CAD, led to the isolation

A novel deletion/inversion mutation in t
A novel deletion/inversion mutation in the low-density lipoprotein receptor gene as a cause of heterozygous familial hypercholesterolemia
✍ Ulla-Maija Koivisto; Kimmo Kontula 📂 Article 📅 1996 🏛 John Wiley and Sons 🌐 English ⚖ 896 KB

## Communicated fq L e n a Peltonen A combined deletiodinversion rearrangement of the LDL receptor gene was discovered in a Finnish patient with heterozygous familial hypercholesterolemia (FH). Sequence analysis of the mutated allele revealed an insertion of 4 nucleotides in exon 11, caused by a c