First LIPA Mutational Analysis in Egyptian Patients Reveals One Novel Variant: Wolman Disease.

Autor: Elaraby NM; Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt. nm.elaraby@nrc.sci.eg., Galal ER; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt., Abdel-Hamid M; Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Elbendary HM; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Elbadry M; Associate Professor of Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt., Mekkawy MK; Human Cytogenetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Ashaat NA; Professor of Genetics and Biotechnology, Ain Shams University, Cairo, Egypt., Mounir SM; Pediatrics Department, Minia University, Minia, Egypt., Ashaat EA; Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Journal of molecular neuroscience : MN [J Mol Neurosci] 2023 Aug; Vol. 73 (7-8), pp. 598-607. Date of Electronic Publication: 2023 Jul 20.
DOI: 10.1007/s12031-023-02139-6
Abstrakt: Lysosomal acid lipase (LAL) is a necessary enzyme for the hydrolysis of both triglycerides (TGs) and cholesteryl esters (CEs) in the lysosome. Deficiency of this enzyme encoded by the lipase A (LIPA) gene leads to LAL deficiency (LAL-D). A severe disease subtype of LAL-D is known as Wolman disease (WD), present with diarrhea, hepatosplenomegaly, and adrenal calcification. Untreated patients do not survive more than a year. The aim of this study was to assess the clinical and molecular characterizations of WD patients in Egypt. A total of seven patients (from five unrelated Egyptian families) were screened by targeted next-generation sequencing (NGS), and the co-segregation of causative variants was analyzed using Sanger sequencing. Furthermore, multiple in silico analyses were performed to assess the pathogenicity of the candidate variants. Overall, we identified three diseases causing variants harbored in the LIPA gene. One of these variants is a novel missense variant (NM_000235.4: c.1122 T > G; p. His374Gln), which was classified as a likely pathogenic variant. All variants were predicted to be disease causing using in silico analyses. Our findings expand the spectrum of variants involved in WD which may help to investigate phenotype-genotype correlation and assist genetic counseling. To the best of our knowledge, this is the first clinico-genetic study carried out on Egyptian patients affected with WD.
(© 2023. The Author(s).)
Databáze: MEDLINE
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