The genetic screening of FXI gene was done by amplifying the gene fragment containing an insertion mutation
; the primers sequence was as reported by Marron et al.
According to reports of known FLNC myopathy families, myocardial involvement occurs in one out of every three FLNC myopathy patients with a W2710X mutation. In China, myocardial involvement occurs in 50% of familial patients with K899-V904 deletion mutation combined with V899-C900 insertion mutation
, and one-third of them have diarrhea. No involvement of the cardiac muscle is reported in c.8107delG and V930-T933 del mutations.
The mutation c.4011insA is an insertion mutation
predicting to lead to a reading frame shift at position 1337 and a stop codon (p.Q1337Qfs*22) and truncate the translation of mRNA resulting in lack of its complete length.
Further analysis revealed that the insertion mutation
caused a complete change of the first transmembrane domain, and deletion of the remaining six transmembrane domains (Figure 3).
By applying direct sequencing of FLCN, we identified a novel deletion mutation (c.668delA/ p.N223TfsX19) and a previously reported insertion mutation
(c.1579_1580insA/p.R527QfsX75) [9-11] of FLCN that might underlie these two families.
In addition to HDR, DSBs can be repaired by nonhomologous end joining (NHEJ), which often generates deletion or insertion mutations
. If a deletion or insertion mutation
causes reading frame shift of a gene, the function of the gene is usually disrupted.
A novel insertion mutation
in the aromatase gene (CYP19A1) was found which caused a frameshift in the open reading frame and a truncation of the protein prior to the heme-binding region.
Genetic analysis revealed four base pair insertion mutation
(c.1114insGAGT) in gene coding cartilage-derived morphogenetic protein-1 (CDMP1).
Among 37 patients the wild type peak of 168 base pairs (bp) was seen in 34 patients (92%) while in addi-tion to wild type peaks another peak of 172 bp showing an insertion mutation
in NPM1 gene was seen in 3 patients (8%) as shown in Fig.
All the mutants had a 4bp insertion mutation
. The wild type fragment appeared on chromatogram at 198bp size (Fig.
Endothelial cell protein c receptor (EPCR) gene exon iii, 23 bp insertion mutation
in the Turkish pediatric thrombotic patients.
A deletion or insertion mutation
could also have drastic consequences, even if it occurred at a point distant to the functional domain, particularly if the insertion or deletion results in a change in the translation reading frame, which can destroy the protein.