uAUG-creating variant in the gene causes mild Familial hypercholesterolemia

Nakazone M, De Marchi M, Pinhel M et al (2009) Effects of APOE, APOB and LDLR variants on serum lipids and lack of association with xanthelasma in individuals from Southeastern Brazil. Genet Mol Biol. 32(2):227–233. https://doi.org/10.1590/S1415-47572009005000028

Alonso R, Perez de Isla L, Muñiz-Grijalvo O et al (2018) Familial hypercholesterolaemia diagnosis and management. Eur Cardiol 13:14–20. https://doi.org/10.15420/ecr.2018:10:2

Article  PubMed  PubMed Central  Google Scholar 

Awan Z, Choi HY, Stitziel N et al (2013) APOE p.Leu167del mutation in familial hypercholesterolemia. Atherosclerosis 231:218–222. https://doi.org/10.1016/j.atherosclerosis.2013.09.007

Article  PubMed  Google Scholar 

Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG (2020) Worldwide prevalence of familial hypercholesterolemia: meta-analyses of 11 million subjects. J Am Coll Cardiol 75:2553–2566. https://doi.org/10.1016/j.jacc.2020.03.057

Article  PubMed  Google Scholar 

Bertolini S, Pisciotta L, Rabacchi C et al (2013) Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy. Atherosclerosis 227:342–348. https://doi.org/10.1016/j.atherosclerosis.2013.01.007

Article  PubMed  Google Scholar 

Cappato S, Divizia MT, Menta L et al (2025) LMX1B haploinsufficiency due to variants in the 5’UTR as a cause of Nail-Patella syndrome. NPJ Genom Med 10:10. https://doi.org/10.1038/s41525-024-00460-6

Article  PubMed  PubMed Central  Google Scholar 

Chora JR, Iacocca MA, Tichý L et al (2022) The clinical genome resource (ClinGen) familial hypercholesterolemia variant curation expert panel consensus guidelines for LDLR variant classification. Genet Med 24:293–306. https://doi.org/10.1016/j.gim.2021.09.012

Article  PubMed  Google Scholar 

Cuchel M, Bruckert E, Ginsberg HN et al (2014) 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. Eur Heart J 35:2146–2157. https://doi.org/10.1093/eurheartj/ehu274

Article  PubMed  PubMed Central  Google Scholar 

Day IN, Whittall RA, O’Dell SD et al (1997) Spectrum of LDL receptor gene mutations in heterozygous familial hypercholesterolemia. Hum Mutat 10:116–127. https://doi.org/10.1002/%28SICI%291098-1004%281997%2910:2%3C116::AID-HUMU4%3E3.0.CO;2-I

De Castro-Orós I, Pampín S, Bolado-Carrancio A et al (2011) Functional analysis of LDLR promoter and 5’ UTR mutations in subjects with clinical diagnosis of familial hypercholesterolemia. Hum Mutat 32:868–872. https://doi.org/10.1002/humu.21520

Article  PubMed  Google Scholar 

Defesche JC, Gidding SS, Harada-Shiba M et al (2017) Familial hypercholesterolaemia. Nat Rev Dis Primers 3:17093. https://doi.org/10.1038/nrdp.2017.93

Article  PubMed  Google Scholar 

den Dunnen JT, Dalgleish R, Maglott DR et al (2016) HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat 37:564–569. https://doi.org/10.1002/humu.22981

Article  Google Scholar 

Di Taranto MD, Giacobbe C, Palma D et al (2021) Genetic spectrum of familial hypercholesterolemia and correlations with clinical expression: implications for diagnosis improvement. Clin Genet 100:529–541. https://doi.org/10.1111/cge.14036

Article  PubMed  PubMed Central  Google Scholar 

Ellingford JM, Ahn JW, Bagnall RD et al (2022) Recommendations for clinical interpretation of variants found in non-coding regions of the genome. Genome Med 14:73. https://doi.org/10.1186/s13073-022-01073-3

Article  PubMed  PubMed Central  Google Scholar 

Filatova AY, Vasilyeva TA, Marakhonov AV et al (2021) Upstream ORF frameshift variants in thePAX65ʹUTR cause congenital aniridia. Hum Mutat 42:1053–1065. https://doi.org/10.1002/humu.24248

Article  PubMed  Google Scholar 

Filatova A, Reveguk I, Piatkova M et al (2023) Annotation of uORFs in the OMIM genes allows to reveal pathogenic variants in 5’utrs. Nucleic Acids Res 51:1229–1244. https://doi.org/10.1093/nar/gkac1247

Article  PubMed  PubMed Central  Google Scholar 

Fouchier SW, Kastelein JJP, Defesche JC (2005) Update of the molecular basis of familial hypercholesterolemia in the Netherlands. Hum Mutat 26:550–556. https://doi.org/10.1002/humu.20256

Article  PubMed  Google Scholar 

Gratton J, Humphries SE, Futema M (2023) Prevalence of FH-causing variants and impact on LDL-C concentration in European, South Asian, and African ancestry groups of the UK Biobank-brief report. Arterioscler Thromb Vasc Biol 43:1737–1742. https://doi.org/10.1161/ATVBAHA.123.319438

Article  PubMed  PubMed Central  Google Scholar 

Khamis A, Palmen J, Lench N et al (2015) Functional analysis of four LDLR 5’UTR and promoter variants in patients with familial hypercholesterolaemia. Eur J Hum Genet 23:790–795. https://doi.org/10.1038/ejhg.2014.199

Article  PubMed  Google Scholar 

Kozak M (1987) Effects of intercistronic length on the efficiency of reinitiation by eucaryotic ribosomes. Mol Cell Biol 7:3438–3445. https://doi.org/10.1128/mcb.7.10.3438-3445.1987

Article  PubMed  PubMed Central  Google Scholar 

Mozas P, Castillo S, Tejedor D et al (2004) Molecular characterization of familial hypercholesterolemia in Spain: identification of 39 novel and 77 recurrent mutations in LDLR. Hum Mutat 24:187. https://doi.org/10.1002/humu.9264

Article  PubMed  Google Scholar 

Reijman MD, Defesche JC, Wiegman A (2023) Genotype-phenotype correlation in a large cohort of pediatric patients with heterozygous and homozygous familial hypercholesterolemia. Curr Opin Lipidol 34:287–295. https://doi.org/10.1097/MOL.0000000000000863

Article  PubMed  PubMed Central  Google Scholar 

Richards S, Aziz N, Bale S et al (2015) 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. Genet Med 17:405–424. https://doi.org/10.1038/gim.2015.30

Article  PubMed  PubMed Central  Google Scholar 

Sample PJ, Wang B, Reid DW et al (2019) Human 5’ UTR design and variant effect prediction from a massively parallel translation assay. Nat Biotechnol 37:803–809. https://doi.org/10.1038/s41587-019-0164-5

Article  PubMed  PubMed Central  Google Scholar 

Simon Broome Registry Group (1991) Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific steering committee on behalf of the Simon Broome register group. BMJ 303:893–896. https://doi.org/10.1136/bmj.303.6807.893

Article  Google Scholar 

Singh S, Bittner V (2015) Familial hypercholesterolemia–epidemiology, diagnosis, and screening. Curr Atheroscler Rep 17:482. https://doi.org/10.1007/s11883-014-0482-5

Article  PubMed  Google Scholar 

Toft-Nielsen F, Emanuelsson F, Benn M (2022) Familial hypercholesterolemia prevalence among ethnicities-systematic review and meta-analysis. Front Genet 13:840797. https://doi.org/10.3389/fgene.2022.840797

Article  PubMed  PubMed Central  Google Scholar 

Warden BA, Fazio S, Shapiro MD (2000) Familial hypercholesterolemia: genes and beyond. In: Feingold KR, Anawalt B, Blackman MR et al (eds) Endotext. MDText.com, Inc., South Dartmouth (MA)

Google Scholar 

Whiffin N, Karczewski KJ, Zhang X et al (2020) Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals. Nat Commun 11:2523. https://doi.org/10.1038/s41467-019-10717-9

Article  PubMed  PubMed Central  Google Scholar 

WHO Human Genetics (1999) This report is dedicated to the memory of professor Roger R. Williams, founder and first chairman. Familial hypercholesterolaemia (FH): report of a second WHO consultation, geneva, 4 September 1998. of the International MED-PED FH Organization https://iris.who.int/handle/10665/66346

Wiegman A, Gidding SS, Watts GF et al (2015) Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 36:2425–2437. https://doi.org/10.1093/eurheartj/ehv157

Article  PubMed  PubMed Central  Google Scholar 

Wikimedia Commons contributors (2022) File:KozakConsensus.jpg. https://commons.wikimedia.org/w/index.php?title=File:KozakConsensus.jpg&oldid=651925609. Accessed 14 Mar 2025

Wright CF, Quaife NM, Ramos-Hernández L et al (2021) Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms. Am J Hum Genet 108:1083–1094. https://doi.org/10.1016/j.ajhg.2021.04.025

Article  PubMed  PubMed Central  Google Scholar 

Zhou Y, Koelling N, Fenwick AL et al (2018) Disruption ofTWIST1translation by 5′ UTR variants in Saethre-Chotzen syndrome. Hum Mutat 39:1360–1365.

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