Author(s)

Angelina Mandadzhieva¹, Daniela Avdzhieva-Tzavella², Tihomir Todorov¹, Savina Tincheva¹, Vanya Sinigerska³, Mariya Ivanova^3,5, Alexey Savov³, Vanyo Mitev⁴, Albena Todorova^1,4

¹Genetic Medico-Diagnostic Laboratory “Genica”, Sofia, Bulgaria.
²Department of Genetics, University Pediatric Hospital, Medical University, Sofia, Bulgaria.
³National Genetic Laboratory, Department of Obstetrics and Gynecology, Faculty of Medicine, Medical University Sofia, Sofia, Bulgaria.
⁴Department of Medical Chemistry and Biochemistry, Medical University Sofia, Sofia, Bulgaria.
⁵Department of Analytical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University “St. Kl. Ohridski”, Sofia, Bulgaria.

Wolman disease is a rare autosomal recessive disorder caused by mutations in the LIPA gene (10q23.31). The LIPA gene encodes lysosomal acid lipase (LAL), which plays a key role in hydrolysis of the cholesteryl esters and triglycerides. Two unrelated families from Bulgaria were referred for genetic testing with clinical diagnosis Wolman disease. Sanger sequencing of all coding exons and exon-intron boundaries of the LIPA gene was performed. The index patients were found to be homozygous for two different mutations in the LIPA gene: a missense mutation, c.260G > T, p.Gly87Val, which affects the enzyme active site and a splice-site change, c.822+1G > A, which most probably destroys the enzyme polypeptide chain. These two completely different types of mutations along the LIPA gene resulted in a very similar phenotype involving liver, kidney, gastrointestinal, muscle and blood disturbances. As consanguinity is not typical for the Bulgarian population, a possible explanation of the homozygosity could be presence of endemic regions for given mutations. To check this hypothesis, selective screening for these mutations was performed in two presumable endemic regions in Bulgaria. Altogether, 100 newborns were screened for p.Gly87Val mutation and the detected carrier frequency was about 1% (1/100), while in the group of 100 newborns screened for the c.822 + 1G > A mutation the detected carrier frequency was 2% (2/100). The results indicate a high recurrence risk of Wolman disease in these particular Bulgarian regions of about 1:10000. These findings are from crucial importance for the inhabitants of the corresponding parts of Bulgaria. They may benefit from early genetic testing and adequate genetic counselling during family planning.

Wolman Disease, LIPA Gene, Lysosomal Acid Lipase, Mutations, Selective Screening

Mandadzhieva, A. , Avdzhieva-Tzavella, D. , Todorov, T. , Tincheva, S. , Sinigerska, V. , Ivanova, M. , Savov, A. , Mitev, V. and Todorova, A. (2017) Wolman Disease in Bulgarian Patients: Selective Genetic Screening in Two Presumable Endemic Regions. American Journal of Molecular Biology, 7, 169-175. doi: 10.4236/ajmb.2017.74013.