Novel mutations of SAR1B gene in four children with chylomicron retention disease
| Autor: | Zarife Kuloğlu, Arzu Meltem Demir, Claudio Rabacchi, Gülin Hizal, Aydan Kansu, Stefano Bertolini, Enza Di Leo, Maria Luisa Simone, Patrizia Tarugi, Sebastiano Calandra, Arzu Ensari |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Malabsorption Apolipoprotein B Endocrinology Diabetes and Metabolism DNA Mutational Analysis Mutation Missense 030204 cardiovascular system & hematology medicine.disease_cause Hypobetalipoproteinemias 03 medical and health sciences Consanguinity 0302 clinical medicine Malabsorption Syndromes Internal medicine Chylomicrons Internal Medicine Medicine Missense mutation Humans Point Mutation SAR1B gene 030212 general & internal medicine Endoscopy Digestive System Intestinal Mucosa Child Recessive hypobetalipoproteinemia Intestinal fat malabsorption Monomeric GTP-Binding Proteins Mutation Nutrition and Dietetics biology business.industry Homozygote Abetalipoproteinemia Infant SAR1B medicine.disease Lipids Pedigree Endocrinology Child Preschool biology.protein Hypobetalipoproteinemia Cardiology and Cardiovascular Medicine business Gene Deletion Chylomicron retention disease |
| Popis: | Background Intestinal lipid malabsorption, resulting from an impaired formation or secretion of chylomicrons and associated with severe hypobetalipoproteinemia (HBL), may be due to biallelic mutations in APOB (homozygous FHBL type-1), MTTP (abetalipoproteinemia), or SAR1B (chylomicron retention disease). Objective We investigated four children, each born from consanguineous parents, presenting with steatorrhea, malnutrition, accumulation of lipids in enterocytes, and severe hypocholesterolemia with an apparent recessive transmission. Methods We sequenced a panel of genes whose variants may be associated with HBL. Results Case 1, a 9-month-old male, was found to be homozygous for a SAR1B variant (c.49 C>T), predicted to encode a truncated Sar1b protein devoid of function (p.Gln17*). Case 2, a 4-year-old male, was found to be homozygous for a SAR1B missense variant [c.409 G>C, p.(Asp137His)], which affects a highly conserved residue close to the Sar1b guanosine recognition site. Case 3, a 6-year-old male, was found to be homozygous for an ∼6 kb deletion of the SAR1B gene, which eliminates exon 2; this deletion causes the loss of the ATG translation initiation codon in the SAR1B mRNA. The same homozygous mutation was found in an 11-month-old child (case 4) who was related to case 3. Conclusions We report 4 children with intestinal lipid malabsorption were found to have chylomicron retention disease due to 3 novel variants in the SAR1B gene. |
| Databáze: | OpenAIRE |
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