PMC9453448_01
PMC9453448_02
PMC9453448_03
PMC9453448_04
Phenotypic (A) and genetic (B) cascade screening. According to phenotypic screening, the younger grandson has HeFH [black-filled square (A)], in relation to genetic screening, he is healthy [white square (B)]. Circles represent females, squares indicate males, and diamond is pregnancy (unknown gender). Black-filled symbols show FH phenotype, gray symbols point to members with an unknown phenotype, and white symbols are healthy family members. Slashes indicate deceased members. +/- or -/- represent heterozygous or wild-type of LDLR-p.K223_D227dup variant. The index patient (II-1) is marked with an arrow. LDL-C, low-density lipoprotein cholesterol; P, pregnancy.
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F1
She also had a high LDL-C level (9.81 mmol/L) but had never taken a LLT (Figure 1A). Despite that phenotypic screening suggested HeFH in two proband's grandsons, the genetic screening made it possible to rule out FH in the younger grandson (Figure 1B).
Genetic analysis of the index patient. (A) Integrated genome view of LDLR-p.K223_D227dup with IGV. (B, C) Electropherograms of LDLR-p.K223_D227dup: (B) sequence from the forward primer, (C) sequence from the reverse primer (reverse complement).
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F2
The validation of this variant was done by Sanger sequencing (Figure 2).