Table 1 Summary of the key clinical genetic data with respect to the 55 LPL frameshift coding variants reported to date

c.10_11insTTCG

p.(Ala117Serfs*61)

[23]

Heterozygote

NI^c

Severe HTG

NI

NI

c.32dup

p.(Ala12Glyfs*29)

This study

Heterozygote

No data

HTG-AP in pregnancy

#1: 33 y (31⁺⁴ weeks of gestation)

#2: 28y (38⁺⁴ weeks of gestation)

#1: Gestational diabetes mellitus at 28 weeks of gestation

#2: negative

c.46_47del

p.(Gln16Glufs*24)

Q-12E > 11X^d

[24]

Heterozygote

NI

Severe HTG

NI

NI

c.77_88 + 1del

p.(Ala26Lysfs*13)

This study

Heterozygote

No data

HTG-AP

43 y

Three years of HTG

c.94_98del

p.(Arg32Phefs*7)

[25]

Heterozygote

NI

HTG

NI

NI

c.128dup

p.(Arg44Lysfs*4)

[26]

Compound heterozygote

p.Asn318Ser (experimentally determined to have 60% wild-type LPL activity by another study [27])

NI

Eruptive cutaneous xanthomata and elevated plasma TG concentration

29 y

Negative

c.133_143del

p.(Thr45Hisfs*3)

11 bp deletion in exon 2

[28]

Compound heterozygote

p.Gly215Glu^e (experimentally determined to have a near complete functional loss of LPL by two studies [29, 30])

 < 1%

Familial chylomicronemia

10 y

Marked HTG at birth

c.133dup

p.(Thr45Asnfs*3)

c.134insA

[31]

Heterozygote

NI

Moderate HTG

41 y

NI

c.183dup

p.(Glu62Argfs*28)

Insertion of an "A" at nucleotide 183 (codon Glu35)

[32]

Homozygote

0

Familial chylomicronemia

5.5 y

Chylomicronemia at 1 month of age after an episode of AP

c.247_249 + 1del

4-bp ACGG deletion at the 3' boundary of exon 2

[33]

Unknown^f

Unknown

LPL deficiency

Unknown

Unknown

c.287_288del

p.(Val96Glyfs*51)

Deletion of nucleotides G²⁸⁶ and T²⁸⁷ in exon 3

[34]

Compound heterozygote

c.440_443del^g

p.(Asn147Thrfs*24)

0

Chylomicronemia

17 y

Manifested with failure to thrive and abdominal pain at age 3 weeks

c.289_294delinsTTTGCCAAAA

p.(Ala97Phefs*52)

Wrongly described as c.289_299delGCCGCCinsTTTGCCAAAA

[35]

Homozygote

NI

Very severe HTG and cerebral dysmorphism

2 m

NI

c.290_293delinsGG

p.(Ala97Glyfs*50)

Deletion of four nucleotides (∆CCGC) and an insertion of two nucleotides (∇GG) at position 290 in exon 3

[36]

Compound heterozygote

p.Leu313Pro^h (experimentally shown to have < 1% of wild-type LPL activity [36])

6.6%

Familial Chylomicronemia

67 y

Eruptive xanthomata and chylomicronemia were noted at the age of 53, during an episode of acute pancreatitis

c.312del

p.(Asp105Thrfs*67)

[37]

Homozygote

0

FCS

3 y

NI

c.334dup

p.(Asp112Glyfs*36)

[38]

Compound heterozygote

p.Arg102Thr (both p.Arg102Thr and p.(Asp112Glyfs*36) were experimentally shown to cause a complete functional loss of LPL [38])

NI

Unexplained fever (“Milky serum” was noticed during laboratory examination)

1 m

c.338_339insAGAGTACCATTCGATAC

p.(Trp113*)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.348_349insAGTACCATTCGACAGTC

p.(Ala117Serfs*61)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.373dup

p.(Ala125Glyfs*23)

c.373_374insG

[39]

Compound heterozygote

p.His273Arg (experimentally determined to have 2% of wild-type LPL activity [39])

NI

Severe HTG

3 y

NI

c.377_378insAGAGTACCATT

p.(Tyr127Glufs*49)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.384delinsTGGGCT

p.(Lys129Glyfs*45)

A six base-pair insertion at the site of a single base deletion, and that the net insertion of five base-pairs at amino acid positions 102 to 103 causes a shift in the reading frame

[40]

Unknown

Unknown

LPL deficiency

Unknown

Unknown

c.386_390del

p.(Lys129Serfs*17)

[31]

Heterozygote

NI

Severe HTG

46 y

NI

c.431_432AG[3]

p.(Glu145Argfs*4)

c.429_430insGAGA

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.438del

p.(Phe146Leufs*26)

[41]

NI

NI

HTG

NI

NI

c.440_443del

p.(Asn147Thrfs*24)

A 4 bp deletion (ACTA) in exon 4

[34]

Compound heterozygote

c.287_288del (described earlier in the Table)

0

Chylomicronemia

17 y

Manifested with failure to thrive and abdominal pain at age 3 weeks

c.483delA

p.(Ala162Profs∗10)

[42]

Heterozygote

NI

Glycogen storage disease type-Ib (severe HTG discovered during laboratory tests)

5 m

Hypoglycemia, hyperlactic acidosis, and sepsis in the neonatal period

c.501_502insGAGAGTACCATTCGAGA

p.(Ala168Glufs*10)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.596del

p.(Ser199Phefs*8)

Deletion of the second nucleotide of codon 172; p.S172fsX179

[43]

Heterozygote

30%

Recurrent hypertriglyceridemic pancreatitis

50 y

Found to be hypertriglyceridemic for 30 years and suffered from four episodes of acute pancreatitis between the ages of 46 y and 49 y

c.599del

p.(Pro200Leufs*7)

[44]

Heterozygote

NI

HTG

NI

NI

c.624del

p.(Leu209Tyrfs*43)

[45]

Heterozygote

NI

NI

NI

NI

c.651del

p.(Gly218Valfs*34)

[35]

Homozygote

NI

Severe HTG

4 y

Pancreatitis at the age 2 y

c.708del

p.(Gly237Valfs*15)

Deletion of the third nucleotide of the codon for Gly209, resulting in termination after 223 residues

[46]

NI

NI

Severe HTG

NI

NI

c.742del

p.(Ala248Leufs*4)

Deletion of a C at base 916

[47]

Homozygote

0 (in both diseased siblings)

Type I hyperlipoproteinemia

NI

Both patients had recurrent episodes of abdominal pain and pancreatitis (age of first disease onset not described)

c.765_766del

p.(Gly256Thrfs*26)

c.765_766delAG

[48]

Homozygote

0 (in two patients from a same family)

Type I hyperlipoproteinemia

#1: 19 y

#2: 32 y

#1: NI

#2: NI

c.767_768insTAAATATT

p.(Gly256_Gly258del)

[20]

Homozygote

NI

HTG-AP

25 y

Central abdominal pain on two occasions in the previous two years; without any other syndromes or diseases

c.769_770insCA

p.(Leu257Profs*8)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.835_836del

p.(Leu279Valfs*3)

[35]

Homozygote

NI

Severe HTG (two patients from a same family)

#1: 37 y

#2: 29 y

#1: NI

#2: Recurrent pancreatitis starting from the age 1 y

c.840del

p.(Asn281Metfs*23)

[35]

Compound heterozygote

Gross deletion of the LPL gene

Familial chylomicronemia

1 m

Had severe HTG, hepatomegaly, lipemia retinalis and eruptive xanthomas

c.899_921dup

p.(Asn308Glyfs*4)

[49]

Homozygote

NI

Severe HTG

NI

HTG since childhood

c.901del

p.(Leu301Serfs*3)

[49]

Heterozygote

23%

Severe HTG

39 y

NI

c.953del

p.(Asn318Ilefs*13)

One nucleotide deletion of A coding Asn 291

[50]

Compound heterozygote

p.Ile221Thrⁱ (almost complete loss of LPL activity [51, 52])

7.5%

Severe HTG

33 y

Suffered from AP several times after drinking alcohol. He did not have diabetes, renal disease, liver disease or hormonal disease. No corneal opacification, xanthomatosis or hepatosplenomegaly were noted

c.1008del

p.(Met336Ilefs*10)

[45]

Heterozygote

NI

NI

NI

NI

c.1010_1011insATTCGAGAGC

p.(Tyr338Phefs*19)

c.1009_1010insCATTCGAGAG

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.1016_1017insC

p.(Lys339Asnfs*15)

AAA → AACA in exon 6

[53]

Heterozygote

NI

HTG (reported in a family; all six variant carriers had HTG while all noncarriers had normal TG levels)

NI

NI

c.1044_1050del

p.(His348Glnfs*43)

[49]

Heterozygote

NI

Severe HTG

52 y

NI

c.1081_1082insAGTA p.(Ala361Glufs*4)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.1107_1108insATTCGAAGAGCGC

p.(Val370Ilefs*9)

c.1106_1107insCATTCGAAGAGCG

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.1115dup

p.(Ser373Glufs*2)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.1119_1120insACCATTC

p.(Glu374Thrfs*11)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.1121_1122insAGAGCGC

p.(Asn375Glufs*10)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.1138_1139del

p.(Leu380Alafs*2)

Deletion CT_1312–1313 that covers the last two bases of exon 7

[54]

Homozygote

0 (in both the proband and his sister)

Severe HTG

Proband: 17.1 y

Sister: 8.9 y

Proband: recurrent episodes of abdominal pain and unexplained diarrhea; acute pancreatitis at age 5 years

Sister: severe HTG

c.1160_1161insT

p.(Lys387Asnfs*26)

[55]

Homozygote

NI

LPL deficiency

NI

NI

c.1163_1164insA

p.(Tyr389Leufs*24)

ACC → ACAC in exon 8

[53]

Heterozygote

NI

HTG (variant carriers had significantly higher TG levels than noncarriers based upon clinical data from 15 variant carriers and 17 noncarriers

NI

NI

c.1303_1304del

p.(Ala435Argfs*12)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.1306_1307insAGTACCATTC

p.(Gly436Glufs*15)

[23]

Heterozygote

NI

Severe HTG

NI

NI

c.1373del

p.(Ala458Aspfs*6)

[56]

Homozygote

NI

LPL deficiency

2 m

Patient exhibited lipemic plasma, lipemia retinalis, hepatomegaly, splenomegaly, and failure to thrive