ABSTRACT
Lysosomal acid lipase deficiency (LALD; MIM#278000) is a continuum of autosomal recessive diseases caused by defects in the gene LIPA and historically divided into two phenotypes: severe infantile-onset form called Wolman disease (WD) and childhood/adult-onset form known as cholesteryl ester storage disease (CESD). We report a novel synonymous homozygous variant c.600Gâ¯>â¯A in LIPA of a patient with LALD. Functional analysis of the patient cDNA and minigene assay revealed this variant as the cause of exonic cryptic splice site activation and 63 b.p. deletion in exon 6. To investigate the impact of this in-frame deletion on protein function, we performed 3D modeling of the human lysosomal acid lipase and showed the alteration of highly conservative region in close proximity to protein active site, which may completely eliminate the enzymatic activity. Using transcript specific real-time quantitative PCR method, we evaluated the relative ratio of the patient's wild type transcript isoform which is significantly reduced and correlates with severe childhood-onset variant of LALD.
Subject(s)
Genetic Variation , Mutation , RNA Splicing , Sterol Esterase/genetics , Wolman Disease/etiology , Wolman Disease/genetics , Adolescent , Child, Preschool , Exons , Female , Humans , Infant , Phenotype , Wolman DiseaseABSTRACT
The case report describes a progressive familial intrahepatic cholestasis II type Byler's syndrome with structural abnormality of the bile canalicular membrane. A child with a rare hereditary pathology,who is on the waiting list for liver transplantation, on the background of complex treatment, including diet therapy, drug therapy achieved a positive dynamics of clinical and laboratory parameters, acceleration of physical, psychomotor and intellectual development, that in general has improved the surgery prognosis and quality of life of the patient.
