Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia

Atherosclerosis
Paola Sabrina BuonuomoSebastiano Calandra

Abstract

Severe hypercholesterolemia associated or not with xanthomas in a child may suggest the diagnosis of homozygous autosomal dominant hypercholesterolemia (ADH), autosomal recessive hypercholesterolemia (ARH) or sitosterolemia, depending on the transmission of hypercholesterolemia in the patient's family. Sitosterolemia is a recessive disorder characterized by high plasma levels of cholesterol and plant sterols due to mutations in the ABCG5 or the ABCG8 gene, leading to a loss of function of the ATP-binding cassette (ABC) heterodimer transporter G5-G8. We aimed to perform the molecular characterization of two children with severe primary hypercholesterolemia. Case #1 was a 2 year-old girl with high LDL-cholesterol (690 mg/dl) and tuberous and intertriginous xanthomas. Case #2 was a 7 year-old boy with elevated LDL-C (432 mg/dl) but no xanthomas. In both cases, at least one parent had elevated LDL-cholesterol levels. For the molecular diagnosis, we applied targeted next generation sequencing (NGS), which unexpectedly revealed that both patients were compound heterozygous for nonsense mutations: Case #1 in ABCG5 gene [p.(Gln251*)/p.(Arg446*)] and Case #2 in ABCG8 gene [p.(Ser107*)/p.(Trp361*)]. Both children had extremely high serum...Continue Reading

Citations

Dec 5, 2019·Biomolecules·Svetlana MikhailovaElena Shakhtshneider
Jul 10, 2018·Current Medicinal Chemistry·Jose María BastidaJosé Ramón González-Porras
Nov 19, 2020·Revista paulista de pediatria : orgão oficial da Sociedade de Pediatria de São Paulo·Luisa Montone Mantovani, Camila Pugliese
Mar 13, 2021·Indian Journal of Hematology & Blood Transfusion : an Official Journal of Indian Society of Hematology and Blood Transfusion·Sudhamsh Reddy DesaiBiju George
Sep 2, 2021·Current Atherosclerosis Reports·Umidakhon MakhmudovaOliver Weingärtner
Dec 10, 2021·Frontiers in Genetics·Libin DengHongbo Xin

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