Familial Hypercholesterolemia (FH) analysis

Familial Hypercholesterolemia (FH) analysis service

TAMM offers cost effective and accredited genetic testing for probands with a clinical diagnosis of Familial Hypercholesterolemia
(FH), as well as performing targeted genetic cascade screening of the relatives.

TAMM’s FH genetic analysis consists of two phases: The first entails the use of a mutation analysis panel using the Agena MassARRAY system and iPLEX Gold chemistry (accredited according to ISO/IEC 17025 by SWEDAC). Samples for which no mutations are found are analyzed using Devyser’s FH v2 amplicon sequencing methodology using Illumina’s MiSeq instrument.

SNP panel test
The Karolinska FH panel investigates 119 known mutations and deletions in the three most important FH genes, LDLR, PCSK9 and APOB using the Agena MassARRAY system and iPLEX Gold chemistry. 

The FH panel was developed by TAMM and it has been successfully validated in collaboration with another Swedish laboratory using samples with known mutations and a proficiency test by the European Molecular Genetics Quality network. With the current
design, the panel detects at least one mutation in approximately 60% of the cases with definitive/probable FH according to the Dutch Lipid Clinic Network diagnostic criteria.

For further information regarding the Karolinska FH panel see “Founder effects facilitate the use of a genotyping-based approach to molecular diagnosis in Swedish patients with familial hypercholesterolaemia” by Benedek et.al., 2021.

The current FH genotyping panel (FH_FM2) consists of:

Gene	Number of mutations
APOB	5
LDLR	111
PCSK9	3

 

The FH panel has been developed by MAF and it has been successfully validated in collaboration with another Swedish laboratory using samples with known mutations and a proficiency test by the European Molecular Genetics Quality network. With the current design, the panel detects at least one mutation in 60% of the cases with definitive/probable FH according to the Dutch Lipid Clinic Network diagnostic criteria.

Amplicon sequencing test
Devyser’s FH kit enables analysis of sequence variants associated with Autosomal Dominant Hypercholesterolemia. Specifically, the assay detects substitutions and INDELS in exons and intron-exon boundaries of the following genes:

LDLR (NM_000527.4)	exon 1-18
PCSK9 (NM_174936.3)	exon 1-12
APOB (NM_000384.3)	exon 26-29