Abstract | BACKGROUND: METHODS AND 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 | Tomoo Okada, Michio Miyashita, Junji Fukuhara, Masahiko Sugitani, Takahiro Ueno, Marie-Elisabeth Samson-Bouma, Lawrence P Aggerbeck |
Journal | Orphanet journal of rare diseases
(Orphanet J Rare Dis)
Vol. 6
Pg. 78
(Nov 21 2011)
ISSN: 1750-1172 [Electronic] England |
PMID | 22104167
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- SAR1B protein, human
- Monomeric GTP-Binding Proteins
|
Topics |
- Asian People
(genetics)
- Biopsy
- Child, Preschool
- Chromosomes, Human, Pair 7
(genetics, metabolism)
- Endoscopy
- Humans
- Hypobetalipoproteinemias
(genetics, metabolism, pathology)
- Intestinal Mucosa
(metabolism)
- Malabsorption Syndromes
(genetics, metabolism, pathology)
- Male
- Monomeric GTP-Binding Proteins
(chemistry, genetics, metabolism)
- Mosaicism
- Phenotype
- Sequence Analysis, DNA
- Silver-Russell Syndrome
(genetics, metabolism, pathology)
- Steatorrhea
(genetics, metabolism, pathology)
- Trisomy
(genetics, pathology)
- Uniparental Disomy
(genetics, pathology)
|