A Form of Metabolic-Associated Fatty Liver Disease Associated with a Novel LIPA Variant

Abstract

Background: The LIPA gene on chromosome 10q23.31 contains 10 exons and encodes lipase A, the lysosomal acid lipase (LAL) containing 399 amino acids. Pathogenic variants in the LIPA result in autosomal recessive Wolman disease and cholesteryl ester storage disease (CESD). Here, we report a novel missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of LIPA in an Iranian family with fatty liver disease identified by whole-exome sequencing and confirmed by Sanger sequencing. Methods: A 28-year-old woman referred with lean NASH cirrhosis and extremely high cholesterol levels. Fatty liver disease was found in six of her family members using vibration-controlled transient elastography (VCTE). Baseline routine laboratory tests were performed and whole-exome sequencing and confirmation by Sanger sequencing were done. Results: The index case had severe dyslipidemia and cirrhosis despite a body mass index of 21.09 kg/m2 . Six other family members had dyslipidemia and fatty liver or cirrhosis. A homozygous missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of LIPA which caused LAL-D was found to be associated with fatty liver disease and/or cirrhosis. Conclusion: A homozygous missense variant (NM_001127605.3:c.928T>A, p.Trp310Arg) of the LIPA gene which caused LAL-D was found to be associated with dyslipidemia, fatty liver disease and/or cirrhosis in six members of an Iranian family. These results should be confirmed by functional studies and extending the study to at least three families.

Genetic and Lifestyle Risk Factors of Metabolic Dysfunction-Associated Fatty Liver Disease and Its Relationship with Premature Coronary Artery Disease: A Study on the Pars Cohort

“… 18 It is necessary to identify the genetic factors associated with hepatic fibrosis and steatosis, especially in adult populations and those who have lean MAFLD. 19 , 20 Despite advances in our understanding of the genetic factors contributing to MAFLD, there is still much to learn about the underlying mechanisms and how to effectively manage this disease…”

“…The identification of genetic factors associated with hepatic fibrosis and steatosis may provide insights into the underlying mechanisms of these conditions and may lead to the development of new therapeutic strategies. 19 , 20 …”

“…The identification of genetic factors associated with hepatic fibrosis and steatosis may provide insights into the underlying mechanisms of these conditions and may lead to the development of new therapeutic strategies. 19,20 The main objective of this study is to identify the risk factors of MAFLD in CAD patients. Through our study, we hope to uncover new insights to identify potential targets for prevention and treatment.…”