دورية أكاديمية
أعرض في EDS

A Novel Variant in the LIPA Gene Associated with Distinct Phenotype.

التفاصيل البيبلوغرافية
العنوان: A Novel Variant in the LIPA Gene Associated with Distinct Phenotype.
المؤلفون: Sarajlija A; Mother and Child Health Care Institute of Serbia 'Dr. Vukan Cupic', Pediatric Day Care Hospital, Belgrade, Serbia.; School of Medicine, University of Belgrade, Belgrade, Serbia., Armengol L; Quantitative Genomic Medicine Laboratories (qGenomics), Esplugues del Llobregat, Spain., Maver A; Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia., Kitic I; Mother and Child Health Care Institute of Serbia 'Dr. Vukan Cupic', Department of Gastroenterology and Hepatology, Belgrade, Serbia.; School of Medicine, University of Belgrade, Belgrade, Serbia., Prokic D; Mother and Child Health Care Institute of Serbia 'Dr. Vukan Cupic', Department of Gastroenterology and Hepatology, Belgrade, Serbia.; School of Medicine, University of Belgrade, Belgrade, Serbia., Cehic M; Mother and Child Health Care Institute of Serbia 'Dr. Vukan Cupic', Pediatric Day Care Hospital, Belgrade, Serbia., Djuricic MS; Mother and Child Health Care Institute of Serbia 'Dr. Vukan Cupic', Department of Clinical Pathology, Belgrade, Serbia.; Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina., Peterlin B; Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia.
المصدر: Balkan journal of medical genetics : BJMG [Balkan J Med Genet] 2023 Mar 01; Vol. 25 (1), pp. 93-100. Date of Electronic Publication: 2023 Mar 01 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Sciendo Country of Publication: Poland NLM ID: 9806959 Publication Model: eCollection Cited Medium: Print ISSN: 1311-0160 (Print) Linking ISSN: 13110160 NLM ISO Abbreviation: Balkan J Med Genet Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: [Warsaw, Poland] : Sciendo
Original Publication: Sofia, Bulgaria : DL&M Ltd., [1998-2001]
مستخلص: Deficiency of lysosomal acid lipase (LAL-D) is caused by biallelic pathogenic variants in the LIPA gene. Spectrum of LAL-D ranges from early onset of hepatosplenomegaly and psychomotor regression (Wolman disease) to a more chronic course (cholesteryl ester storage disease - CESD). The diagnosis is based on lipid and biomarker profiles, specific liver histopathology, enzyme deficiency, and identification of causative genetic variants. Biomarker findings are a useful for diagnostics of LAL-D, including high plasma concentration of chitotriosidase as well as elevated oxysterols. Current treatment options include enzyme replacement therapy (sebelipase-alpha), statins, liver transplantation, and stem cell transplantation. We present two pairs of siblings from Serbia with a distinctive phenotype resembling LAL-D with a novel variant of unknown significance (VUS) detected in the LIPA gene and residual LAL activity. All patients presented with hepatosplenomegaly at early childhood. In siblings from family 1, compound heterozygosity for a pathogenic c.419G>A (p.Trp140Ter) variant and a novel VUS c.851C>T (p.Ser284Phe) was detected. Patients from family 2 were homozygous for c.851C>T VUS and both have typical histopathologic findings for LAL-D in the liver. Enzyme activity of LAL was tested in three patients and reported as sufficient, and therefore enzyme replacement therapy could not be approved. When confronted with a challenge of diagnosing an inherited metabolic disorder, several aspects are taken into consideration: clinical manifestations, specific biomarkers, enzyme assay results, and molecular genetic findings. This report brings cases to light which have a considerable discrepancy between those aspects, namely the preserved LAL enzyme activity in presence of clinical manifestations and rare variants in the LIPA gene.
Competing Interests: Conflict of interest Conflict of interest statement: All authors declare that they have no conflict of interest.
(© 2022 Sarajlija A., Armengol L., Maver A., Kitic I., Prokic D., Cehic M., Djuricic M.S., Peterlin B., published by Sciendo.)
References: Acta Paediatr Suppl. 2005 Mar;94(447):43-6; discussion 37-8. (PMID: 15895711)
Drug Des Devel Ther. 2020 Feb 11;14:591-601. (PMID: 32103901)
J Am Coll Cardiol. 2007 Dec 18;50(25):2399-403. (PMID: 18154965)
Lancet Gastroenterol Hepatol. 2017 Sep;2(9):670-679. (PMID: 28786388)
J Inherit Metab Dis. 2019 May;42(3):509-518. (PMID: 30684275)
PLoS One. 2018 Jul 6;13(7):e0200008. (PMID: 29979746)
Orphanet J Rare Dis. 2021 Jan 6;16(1):13. (PMID: 33407676)
Hum Genet. 2017 Jun;136(6):665-677. (PMID: 28349240)
Obesity (Silver Spring). 2012 Oct;20(10):2075-82. (PMID: 22395809)
Clin Chem. 2018 Apr;64(4):690-696. (PMID: 29339442)
J Clin Lipidol. 2015 Sep-Oct;9(5):716-26.e1. (PMID: 26350820)
Clin Chim Acta. 2017 Aug;471:201-205. (PMID: 28532785)
Hum Mutat. 2019 Nov;40(11):2007-2020. (PMID: 31180157)
Mol Genet Metab. 2012 Mar;105(3):450-6. (PMID: 22227072)
Hepatology. 2013 Sep;58(3):958-65. (PMID: 23424026)
Histopathology. 2012 Jun;60(7):1107-13. (PMID: 22621222)
J Neurochem. 2016 Nov;139(3):456-470. (PMID: 27453211)
J Lipid Res. 2016 Mar;57(3):361-7. (PMID: 26733147)
Clin J Am Soc Nephrol. 2008 Jan;3(1):139-45. (PMID: 18003767)
Hum Mol Genet. 2019 Sep 15;28(18):3043-3052. (PMID: 31131398)
Int J Mol Sci. 2020 Apr 14;21(8):. (PMID: 32295281)
Atherosclerosis. 2014 Jul;235(1):21-30. (PMID: 24792990)
Atherosclerosis. 2015 Oct;242(2):443-9. (PMID: 26291497)
Atherosclerosis. 2017 Oct;265:124-132. (PMID: 28881270)
Eur J Biochem. 1994 Feb 1;219(3):905-14. (PMID: 8112342)
JIMD Rep. 2017;37:7-12. (PMID: 28220406)
J Pediatr Gastroenterol Nutr. 2013 Jun;56(6):682-5. (PMID: 23403440)
Am J Hum Genet. 2000 Feb;66(2):378-92. (PMID: 10677297)
J Hepatol. 2019 Jan;70(1):142-150. (PMID: 30315827)
J Hepatol. 2013 Jun;58(6):1230-43. (PMID: 23485521)
Srp Arh Celok Lek. 2001 Jul-Aug;129(7-8):207-10. (PMID: 11797452)
J Hepatol. 1999 Oct;31(4):741-6. (PMID: 10551400)
JIMD Rep. 2017;31:15-27. (PMID: 27008195)
J Clin Gastroenterol. 1991 Aug;13(4):482-5. (PMID: 1918862)
Appl Clin Genet. 2016 Oct 17;9:157-167. (PMID: 27799810)
Genomics. 1996 Apr 1;33(1):85-93. (PMID: 8617513)
فهرسة مساهمة: Keywords: LIPA; lysosomal acid lipase deficiency; variant of uncertain significance
تواريخ الأحداث: Date Created: 20230307 Latest Revision: 20230308
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9985358
DOI: 10.2478/bjmg-2022-0010
PMID: 36880034
قاعدة البيانات: MEDLINE
الوصف
تدمد:1311-0160
DOI:10.2478/bjmg-2022-0010