Journal ArticleDOI
Lipid profile and genetic status in a familial hypercholesterolemia pediatric population: exploring the LDL/HDL ratio.
Maria Donata Di Taranto,Renato de Falco,Ornella Guardamagna,Giulia Massini,Carola Giacobbe,Renata Auricchio,Basilio Malamisura,Michela Proto,Daniela De Palma,Luigi Greco,Giuliana Fortunato +10 more
TLDR
The LDL/HDL ratio proved to be a better parameter than LDL-C for discriminating patients with from patients without mutations across different genetic statuses, and gradually increased from patients with missense mutations, null mutations and compound heterozygotes.Abstract:
Background Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in genes involved in low-density lipoprotein (LDL) uptake (LDLR, APOB and PCSK9). Genetic diagnosis is particularly useful in asymptomatic children allowing for the detection of definite FH patients. Furthermore, defining their genetic status may be of considerable importance as the compound heterozygous status is much more severe than the heterozygous one. Our study aims at depicting the genetic background of an Italian pediatric population with FH focusing on the correlation between lipid profile and genetic status. Methods Out of 196 patients with clinically suspected FH (LDL-cholesterol [LDL-C] levels above 3.37 mmol/L, cholesterol level above 6.46 mmol/L in a first-degree relative or the presence of premature cardiovascular acute disease in a first/second-degree relative), we screened 164 index cases for mutations in the LDLR, APOB and PCSK9 genes. Results Patients with mutations (129/164) showed increased levels of LDL-C, 95th percentile-adjusted LDL-C and LDL/high-density lipoprotein (HDL) ratio and decreased levels of HDL-C, adjusted HDL-C. The association of the LDL/HDL ratio with the presence of mutations was assessed independently of age, (body mass index) BMI, parental hypercholesterolemia, premature coronary artery disease (CAD), triglycerides by multivariate logistic regression (odds ratio [OR]=1.701 [1.103-2.621], p=0.016). The LDL/HDL ratio gradually increased from patients without mutations to patients with missense mutations, null mutations and compound heterozygotes. Conclusions In conclusion, the LDL/HDL ratio proved to be a better parameter than LDL-C for discriminating patients with from patients without mutations across different genetic statuses.read more
Citations
More filters
Journal ArticleDOI
Familial hypercholesterolemia: A complex genetic disease with variable phenotypes
TL;DR: Patients with a null variant in LDLR gene showed higher LDL-cholesterol levels and higher risk for coronary artery disease than patients with a defective variant, and pathogenic variants in several lipid-related genes causing different dyslipidemias were found among FH patients.
Journal ArticleDOI
A Real-World Experience of Clinical, Biochemical and Genetic Assessment of Patients with Homozygous Familial Hypercholesterolemia
Maria Donata Di Taranto,Carola Giacobbe,Alessio Buonaiuto,Ilenia Calcaterra,Daniela De Palma,Giovanna Maione,Gabriella Iannuzzo,Matteo Nicola Dario Di Minno,Paolo Rubba,Giuliana Fortunato +9 more
TL;DR: Homozygous familial hypercholesterolemia patients showed higher basal LDL-cholesterol and a poorer response to therapy compared with compound heterozygotes, highlighting the role of genetic screening in differentiating one genetic status from the other.
Journal ArticleDOI
Age-related changes of cholestanol and lathosterol plasma concentrations: an explorative study.
Monica Gelzo,Maria Donata Di Taranto,Concetta Sica,Antonio Boscia,Francesco Papagni,Giuliana Fortunato,Gaetano Corso,Antonio Dello Russo +7 more
TL;DR: Several differences of plasma cholestanol and lathosterol levels and their ratios to cholesterol levels among newborns, children and adults are revealed, which indicate the need of age-related reference values of cholanol and lATHosterol concentrations, including also newborns and children.
Journal ArticleDOI
Identification of novel variants in the LDLR gene in Russian patients with familial hypercholesterolemia using targeted sequencing
V. V. Miroshnikova,Olga V. Romanova,O N Ivanova,Mikhail A. Fedyakov,A A Panteleeva,Yury A. Barbitoff,Maria V. Muzalevskaya,Sorejya A. Urazgildeeva,Victor S. Gurevich,Stanislav P. Urazov,Sergey G. Scherbak,Andrey M. Sarana,Natalia A. Semenova,Inga V. Anisimova,Darya M. Guseva,S.N. Pchelina,Andrey S. Glotov,Ekaterina Y. Zakharova,Oleg S. Glotov +18 more
TL;DR: Seven novel LDLR variants considered to be pathogenic or likely pathogenic were reported, and four missense variants were located in the coding regions, which corresponded to functional protein domains, and two frameshifts were identified that produced truncated proteins.
Journal ArticleDOI
Genetic spectrum of familial hypercholesterolemia and correlations with clinical expression: Implications for diagnosis improvement.
Maria Donata Di Taranto,Carola Giacobbe,Daniela De Palma,Gabriella Iannuzzo,Marco Gentile,Ilenia Calcaterra,Ornella Guardamagna,Renata Auricchio,Matteo Nicola Dario Di Minno,Giuliana Fortunato +9 more
TL;DR: In this article, the authors performed a retrospective analysis of a genetically screened population (528 unrelated patients - 342 adults and 186 children) to evaluate the biochemical and clinical correlations with the different genetic statuses.
References
More filters
Journal ArticleDOI
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
Sue Richards,Nazneen Aziz,Nazneen Aziz,Sherri J. Bale,David P. Bick,Soma Das,Julie M. Gastier-Foster,Wayne W. Grody,Madhuri Hegde,Elaine Lyon,Elaine B. Spector,Karl V. Voelkerding,Heidi L. Rehm +12 more
TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.
2000 CDC Growth Charts for the United States: methods and development.
Robert J. Kuczmarski,Cynthia L. Ogden,Shumei S. Guo,Laurence M. Grummer-Strawn,Katherine M. Flegal,Zuguo Mei,Rong Wei,Lester R. Curtin,Alex F. Roche,Clifford L. Johnson +9 more
TL;DR: The 2000 CDC growth charts were developed with improved data and statistical procedures and now have an instrument for growth screening that better represents the racial-ethnic diversity and combination of breast- and formula-feeding in the United States.
Journal ArticleDOI
Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society
Børge G. Nordestgaard,M. John Chapman,Steve E. Humphries,Henry N. Ginsberg,Luis Masana,Olivier S. Descamps,Olov Wiklund,Robert A. Hegele,Frederick J. Raal,Joep C. Defesche,Albert Wiegman,Raul D. Santos,Gerald F. Watts,Klaus G. Parhofer,G. Kees Hovingh,Petri T. Kovanen,Catherine Boileau,Maurizio Averna,Jan Borén,Eric Bruckert,Alberico L. Catapano,Jan Albert Kuivenhoven,Jan Albert Kuivenhoven,P. Pajukanta,Kausik K. Ray,Anton F. H. Stalenhoef,Erik S.G. Stroes,Marja-Riitta Taskinen,Anne Tybjærg-Hansen +28 more
TL;DR: There is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition, familial hypercholesterolaemia.
Journal ArticleDOI
Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society
Marina Cuchel,Eric Bruckert,Henry N. Ginsberg,Frederick J. Raal,Raul D. Santos,Robert A. Hegele,Jan Albert Kuivenhoven,Børge G. Nordestgaard,Olivier S. Descamps,Elisabeth Steinhagen-Thiessen,Anne Tybjærg-Hansen,Gerald F. Watts,Maurizio Averna,Catherine Boileau,Jan Borén,A.L. Catapano,Joep C. Defesche,G. Kees Hovingh,Steve E. Humphries,Petri T. Kovanen,Luis Masana,Päivi Pajukanta,Klaus G. Parhofer,Kausik K. Ray,Anton F. H. Stalenhoef,Erik S.G. Stroes,Marja-Riitta Taskinen,Albert Wiegman,Olov Wiklund,M. John Chapman +29 more
TL;DR: In this article, the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH.