Academy of Medical Sciences of I.R. Iran Archives of Iranian Medicine 1029-2977 26 2 2023 02 01 A Form of Metabolic-Associated Fatty Liver Disease Associated with a Novel LIPA Variant 86 91 10.34172/aim.2023.14 EN Amir Anushiravani https://orcid.org/0000-0002-9196-1901 Hossein Jafari Khamirani https://orcid.org/0000-0001-7703-7387 Ashraf Mohamadkhani Arya Mani Mehdi Dianatpour https://orcid.org/0000-0003-1217-9477 Reza Malekzadeh https://orcid.org/0000-0002-9820-6335 Journal Article 10.34172/aim.2023.14 2022 11 15 2022 11 16 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.