Table 1
Off-treatment characteristics and lipid profile of the studied families. The names of families described in this report are anonymised.
| Family | FN1 family | FN4A family | ||||||
|---|---|---|---|---|---|---|---|---|
| Family members | Proband 1 | Father | Mother | Sister | Brother | Brother | Proband 2 | Brother |
| Code | FN1* | FN1A | FN1B | FN1C | FN1D | FN1E | FN4A* | FN4B |
| Sex | M | M | F | F | M | M | M | M |
| Age | 16 | 51 | 51 | 18 | 14 | 8 | 29 | 36 |
| Total Cholesterol | 19.12 | NA | 7.53 | 6.2 | 6.84 | 3.55 | 11.11 | 8.57 |
| Triglyceride | 2.24 | NA | 1.01 | 0.48 | 0.56 | 0.88 | 0.54 | 0.63 |
| LDL-C | 13.1 | NA | 5.48 | 4.1 | 4.83 | 1.95 | 9.0 | 6.08 |
| HDL-C | 0.78 | NA | 1.25 | 1.29 | 1.11 | 1.22 | 0.81 | 1.5 |
| Clinical signs | Bilateral Xanthomas, Arcus lipoides | No | No | No | No | No | Bilateral Xanthomas, Arcus lipoides, IHD had stents to coronaries | No |
| Medication | LDL apheresis, Atorvastatin, Ezetemibe | Atorvastatin | Atorvastatin | Atorvastatin | Atorvastatin | None | LDL apheresis, Atorvastatin, Ezetemibe | Atorvastatin, Ezetimibe |
| Family history of CAD | Unknown | Unknown | Unknown | Unknown | Unknown | Unknown | Yes | Yes |
[i] Legend: Normal range for lipid profiles was described in our recent publication (Al-Allaf et al., 2016a). IHD; Ischaemic heart disease. * Index case.
Figure 1
Clinical presentations of patient FN1. Pictures A–D taken when he was 15 years old. Picture E–F taken when he was 18 years old. A) Skin xanthoma, right elbow excised. B) Xanthoma tendinosum left elbow. C) Arcus lipoides, right eye. D) Arcus lipoides, left eye. E) Skin xanthoma, right elbow disappearance after LDL apheresis. F) Skin xanthoma, left elbow disappearance after LDL apheresis.
Figure 2
Clinical presentations of patient FN4A. A) Xanthoma tendinosum right elbow excised. B) Xanthoma tendinosum left elbow. C) Arcus lipoides. D) Xanthoma tendinosum left foot. E) Xanthoma tendinosum right foot. F) Xanthoma tendinosum disappearance after LDL apheresis. G) Interphalangeal Xanthomas feet. H) Interphalangeal Xanthomas feet after LDL apheresis. I) Interphalangeal Xanthomas hand. J) Interphalangeal Xanthomas hand after LDL apheresis. K) Left Anterior Descending (LAD): mid segment significant lesion (white arrow). L) Left Anterior Descending (LAD): post Percutaneous Coronary Intervention and stenting (white arrow). M) Right Coronary Artery (RCA) totally occluded proximally (white arrow). N) Right Coronary Artery (RCA): post Percutaneous Coronary Intervention and stenting (white arrow).
Figure 3
A recurrent frameshift mutation [c.2027delG, p.(G676Afs*33)] identified in exon 14 of the LDLR gene. A) Pedigree of the families FN1. B) Pedigree of the families FN4A. C) Representative DNA sequence from a healthy control (Wild type; WT) and heterozygous (Htz) and homozygous (Hmz) of each family. Filled symbols indicate Hmz, half filled indicates Htz, crossed line indicates patients had died and unfilled indicates un-affected individual. ? = NOT available for DNA analysis. * Proband.
Table 2
Overview of targeted genes variants identified by Ion-torrent PGM.
| Samples | Gene | Zygosity | Coding region changes | Amino acid changes | Variant type | Exon | dnSNP | SIFT | Provean | PolyPhen-2 |
|---|---|---|---|---|---|---|---|---|---|---|
| FN1 | LDLR | Homozygous | c.2027delG | p.(G676Afs*33) | Frameshift | 14 | Al-Allaf et al., 2016a | n/a | n/a | n/a |
| APOB | Heterozygous | c.9937C>A | p.(L3313I) | Missense | 26 | rs146687604 | Damaging | Neutral | Possibly damaging | |
| APOB | Heterozygous | c.3634C>A | p.(L1212M) | Missense | 23 | rs61736761 | Tolerated | Neutral | Possibly damaging | |
| APOB | Heterozygous | c.2937C>T | – | coding-synon | 19 | rs145649470 | – | – | – | |
| ABCA1 | Heterozygous | c.6183C>T | – | coding-synon | 46 | rs9282537 | – | – | – | |
| ABCA1 | Heterozygous | c.3684G>A | – | coding-synon | 25 | rs2230807 | – | – | – | |
| ABCA1 | Heterozygous | c.3364C>T | – | coding-synon | 23 | rs35204915 | – | – | – | |
| ABCA1 | Homozygous | c.2040C>A | – | coding-synon | 15 | rs2853579 | – | – | – | |
| LPL | Heterozygous | c.207G>A | – | coding-synon | 4 | rs248 | – | – | – | |
| FN4A | LDLR | Homozygous | c.2027delG | p.(G676Afs*33) | Frameshift | 14 | Al-Allaf et al., 2016a | n/a | n/a | n/a |
| ABCA1 | Heterozygous | c.936C>T | – | coding-synon | 9 | rs2274873 | – | – | – | |
| APOC3 | Heterozygous | c.55C>T | p.(R19*) | Nonsense | 2 | rs76353203 | n/a | n/a | n/a | |
| PON2 | Homozygous | c.248G>A | p.(G83Q) | Missense | 4 | Novel | Damaged | Deleterious | – | |
| LPL | Heterozygous | c.1421C>G | p.(S474*) | Nonsense | 9 | rs328 | n/a | n/a | n/a |
[i] Legend: n/a: not applicable.