Diagnosis of Familial Hypercholesterolemia in Children and Young Adults
Abstract
:1. Introduction
2. Results
2.1. The Main Characteristics of the Study Sample
2.2. Results of Molecular Genetic Analyses of Children with FH
2.3. A Clinical Case
2.4. Results of the Molecular Genetic Testing of Young Adults with FH
2.5. Treatment of Patients under the Age of 18 with FH
3. Discussion
4. Materials and Methods
4.1. The Study Sample
4.2. Molecular Genetic Analysis
4.3. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
CHD | coronary heart disease |
CVD | cardiovascular disease |
DLCN | Dutch Lipid Clinic Network |
FH | familial hypercholesterolemia |
HDL-C | high-density lipoprotein cholesterol |
heFH | heterozygous familial hypercholesterolemia |
hoFH | homozygous familial hypercholesterolemia form |
LDL-C | low-density lipoprotein cholesterol |
Me | median |
MLPA | multiplex ligation-dependent probe amplification |
TC | total cholesterol |
TG | triglyceride |
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Parameter | Age Groups | p | |
---|---|---|---|
<18 Years | 18–44 Years | ||
Number of subjects | 17 | 43 | - |
Men, n (%) | 5 (29) | 15 (35) | 0.047 |
Age, years, Me [25th; 75th] | 10 [7.5; 14] | 35 [28; 39] | <0.001 |
Family history of CVDs, n (%) | 16 (94) | 38 (88) | <0.001 |
Body-mass index, kg/m2 | 19.3 [16.4; 23.2] | 23.7 [21.6; 28.0] | 0.008 |
Tendon xanthomas, n (%) | 2 (12) | 10 (23) | <0.001 |
Arterial atherosclerosis, n (%) | - | 12 (28) | <0.001 |
Maximum level of TC the patient, mmol/L, Me [25th; 75th] | 8.6 [6.6; 10.69] | 9.4 [8.0; 10.96] | 0.199 |
TC, mmol/L, Me [25th; 75th] | 8.05 [6.43; 9.98] | 8.24 [6.8; 10.2] | 0.525 |
LDL-C, mmol/L, Me [25th; 75th] | 5.85 [4.15; 7.55] | 5.73 [4.84; 7.31] | 0.717 |
HDL-C, mmol/L, Me [25th; 75th] | 1.44 [1.17; 1.66] | 1.39 [1.07; 1.91] | 0.925 |
TG, mmol/L, Me [25th; 75th] | 0.68 [0.55; 0.91] | 1.08 [0.82; 1.93] | 0.005 |
Lipoprotein a, mg/dL, Me [25th; 75th] | 16.8 [14.1; 31.2] | 23.7 [20.3; 65.1] | 0.245 |
Patient ID | Position Number in the Reference Sequence | Gene | Position on Chromosome (GRCh38) | Nucleotide Substitution | Amino Acid Replacement | Minor Allele Frequency (MAF) According to the GnomAD Database | Clinical Significance According to the ClinVar Database |
---|---|---|---|---|---|---|---|
P82 | rs121908038 | LDLR | 19:11113293 | c.1202T>A | p.Leu401His | ND | Likely pathogenic |
P60 | rs879254566 | LDLR | 19:11105440 | c.534TT>G | p.Asp178Glu | ND | Pathogenic/likely pathogenic |
P55 | rs879254721 | LDLR | 19:11107496 | c.922G>A | p.Glu308Lys | ND | Pathogenic |
P4, P6, P7 | rs879254980 | LDLR | 19:11116179 | c.1672G>T | p.Glu558Ter | ND | Pathogenic |
P36, P37 | rs879255191 | LDLR | 19:11128090 | c.2389+5G>A | - | ND | Conflicting interpretations of pathogenic/likely pathogenic |
P73 | rs570942190 | LDLR | 19:11113337 | c.1246C>T | p.Arg416Trp | T = 0.000007 | Not reported in ClinVar |
P22 | rs5742904 | APOB | 2:21006288 | c.10580G>A | p.Arg3527Gln | T = 0.000275 | Pathogenic |
P95 | rs145164937 | ABCG5 | 2:43832056 | c.293C>G | p.Ala98Gly | C = 0.002223 | Conflicting interpretations of pathogenicity/likely pathogenic |
Subject ID | Position No. in Reference Sequence | Gene | Position on Chromosome (GRCh38) | Nucleotide Substitution | Amino Acid Substitution | Minor Allele Frequency (MAF) According to GnomAD | Clinical Significance According to ClinVar |
---|---|---|---|---|---|---|---|
P5 | rs879254980 | LDLR | 19:11116179 | c.1672G>T | p.Glu558Ter | ND | Pathogenic |
P34, P53 | rs28942078 | LDLR | 19:11113376 | c.1285G>A | p.Val429Met | A = 0.000012 | Pathogenic |
P38, P39 | rs879255191 | LDLR | 19:11128090 | c.2389+5G>A | - | ND | Conflicting interpretations of pathogenic/likely pathogenic |
P50 | NM_000527.4:c.(67+1_68-1)_(1586+1_1587-1)del | LDLR | - | - | - | ND | Eliminated a region spanning exons 2 to 10 |
P57, P58, P81, P103 | rs121908038 | LDLR | 19:11113293 | c.1202T>A | p.Leu401His | ND | Likely pathogenic |
P65 | rs137853964 | LDLR | 19:11129602 | c.2479G>A | p.Val827Ile | A = 0.001006 | Likely pathogenic |
P70 | rs570942190 | LDLR | 19:11113337 | c.1246C>T | p.Arg416Trp | T = 0.000024 | Not reported in ClinVar |
P78 | rs875989907 | LDLR | 19:11106666 | c.796G>A | p.Asp266Asn | A = 0.000012 | Pathogenic |
rs879254769 | LDLR | 19:11110765 | c.1054T>C | p.Cys352Ser | ND | Likely pathogenic | |
P90 | rs755757866 | LDLR | 19:11110730 | c.1019G>T | p.Cys340Tyr | T = 0.000008 | Likely pathogenic |
P76 | rs2147257524 | LDLR | 19:11116909 | c.1756T>C | p.Ser586Pro | ND | Likely pathogenic |
P23 | rs773328511 | LDLR | 19:11106680 | c.810C>A | p.Cys270Ter | T = 0.000008 | Pathogenic |
P25, P94 | rs5742904 | APOB | 2:21006288 | c.10580G>A | p.Arg3527Gln | T = 0.000275 | Pathogenic |
P96 | rs145164937 | ABCG5 | 2:43832056 | c.293C>G | p.Ala98Gly | C = 0.002223 | Conflicting interpretations of pathogenicity/likely pathogenic |
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Share and Cite
Timoshchenko, O.; Ivanoshchuk, D.; Semaev, S.; Orlov, P.; Zorina, V.; Shakhtshneider, E. Diagnosis of Familial Hypercholesterolemia in Children and Young Adults. Int. J. Mol. Sci. 2024, 25, 314. https://doi.org/10.3390/ijms25010314
Timoshchenko O, Ivanoshchuk D, Semaev S, Orlov P, Zorina V, Shakhtshneider E. Diagnosis of Familial Hypercholesterolemia in Children and Young Adults. International Journal of Molecular Sciences. 2024; 25(1):314. https://doi.org/10.3390/ijms25010314
Chicago/Turabian StyleTimoshchenko, Olga, Dinara Ivanoshchuk, Sergey Semaev, Pavel Orlov, Valentina Zorina, and Elena Shakhtshneider. 2024. "Diagnosis of Familial Hypercholesterolemia in Children and Young Adults" International Journal of Molecular Sciences 25, no. 1: 314. https://doi.org/10.3390/ijms25010314
APA StyleTimoshchenko, O., Ivanoshchuk, D., Semaev, S., Orlov, P., Zorina, V., & Shakhtshneider, E. (2024). Diagnosis of Familial Hypercholesterolemia in Children and Young Adults. International Journal of Molecular Sciences, 25(1), 314. https://doi.org/10.3390/ijms25010314