title: Anderson's disease/chylomicron retention disease in a Japanese patient with uniparental disomy 7 and a normal SAR1B gene protein coding sequence.
abstract: BACKGROUND
  Anderson's Disease (AD)/Chylomicron Retention Disease (CMRD) is a rare hereditary hypocholesterolemic disorder characterized by a malabsorption syndrome with steatorrhea, failure to thrive and the absence of chylomicrons and apolipoprotein B48 post-prandially. All patients studied to date exhibit a mutation in the SAR1B gene, which codes for an essential component of the vesicular coat protein complex II (COPII) necessary for endoplasmic reticulum to Golgi transport. We describe here a patient with AD/CMRD, a normal SAR1B gene protein coding sequence and maternal uniparental disomy of chromosome 7 (matUPD7).
  
  
  RESULTS
  The patient, one of two siblings of a Japanese family, had diarrhea and steatorrhea beginning at five months of age. There was a white duodenal mucosa upon endoscopy. Light and electron microscopy showed that the intestinal villi were normal but that they had lipid laden enterocytes containing accumulations of lipid droplets in the cytoplasm and lipoprotein-size particles in membrane bound structures. Although there were decreased amounts in plasma of total- and low-density lipoprotein cholesterol, apolipoproteins AI and B and vitamin E levels, the triglycerides were normal, typical of AD/CMRD. The presence of low density lipoproteins and apolipoprotein B in the plasma, although in decreased amounts, ruled out abetalipoproteinemia. The parents were asymptomatic with normal plasma cholesterol levels suggesting a recessive disorder and ruling out familial hypobetalipoproteinemia. Sequencing of genomic DNA showed that the 8 exons of the SAR1B gene were normal. Whole genome SNP analysis and karyotyping revealed matUPD7 with a normal karyotype. In contrast to other cases of AD/CMRD which have shown catch-up growth following vitamin supplementation and a fat restricted diet, our patient exhibits continued growth delay and other aspects of the matUPD7 and Silver-Russell Syndrome phenotypes.
  
  
  CONCLUSIONS
  This patient with AD/CMRD has a normal SAR1B gene protein coding sequence which suggests that factors other than the SAR1B protein may be crucial for chylomicron secretion. Further, this patient exhibits matUPD7 with regions of homozygosity which might be useful for elucidating the molecular basis of the defect(s) in this individual. The results provide novel insights into the relation between phenotype and genotype in these diseases and for the mechanisms of secretion in the intestine.
authors: Department of Pediatrics, Nihon University School of Medicine, 30-1 Oyaguchi Kamicho Itabashi-ku, Tokyo 173-8630, Japan. tomo@med.email.ne.jp
authors: Tomoo
authors: T
authors: Okada
authors: Michio
authors: M
authors: Miyashita
authors: Junji
authors: J
authors: Fukuhara
authors: Masahiko
authors: M
authors: Sugitani
authors: Takahiro
authors: T
authors: Ueno
authors: Marie-Elisabeth
authors: ME
authors: Samson-Bouma
authors: Lawrence P
authors: LP
authors: Aggerbeck
mesh_terms: D044466:Asian People / Q000235:genetics; D001706:Biopsy; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics / Q000378:metabolism; D004724:Endoscopy; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism; D008286:Malabsorption Syndromes / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009030:Mosaicism; D010641:Phenotype; D017422:Sequence Analysis, DNA; D056730:Silver-Russell Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045602:Steatorrhea / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014314:Trisomy / Q000235:genetics / Q000473:pathology*; D024182:Uniparental Disomy / Q000235:genetics / Q000473:pathology*
chemical_list: C513282:SAR1B protein, human; D020559:Monomeric GTP-Binding Proteins