Novel mutations of SAR1B gene in four children with chylomicron retention disease

Simone M. L., Rabacchi C., KULOĞLU Z., Kansu A., ENSARİ A., DEMİR A. M., ...Daha Fazla

Journal of Clinical Lipidology, cilt.13, sa.4, ss.554-562, 2019 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 13 Sayı: 4
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.jacl.2019.05.013
  • Dergi Adı: Journal of Clinical Lipidology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.554-562
  • Anahtar Kelimeler: Recessive hypobetalipoproteinemia, Chylomicrons, Intestinal fat malabsorption, SAR1B gene, Consanguinity
  • Sağlık Bilimleri Üniversitesi Adresli: Evet

Özet

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.