Defect in lung growth Comparative study of three diagnostic criteria.

Traduction anglaise de l'article Arch Pediatr. 2004 Jun;11(6):515-7 Référence pubmed : 15158815A systematic analysis was made of the autopsies of 74 newborns and fetuses (49 pathological cases and 25 controls) to detect defects in lung growth. In each case lung/body (L/B) weight ratio was calculated, and radial alveolar (RA) count and histological assessment were performed. The L/B ratio is of diagnostic value when lower than 0.012 but not when there is intercurrent disease. RA count is low in lung hypoplasia but is not an entirely reliable diagnostic criterion since it change throughout pregnancy and the earlier the gestational age the wider the range of variation. Histological assessment showed an abnormally high number of bronchi and bronchi in distal location with in some cases delayed differentiation of distal airways. If any one of the above three critera fails to determine lung hypoplasia the other two can be used to arrive at diagnosis

Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome).

Contains fulltext : 48537.pdf (publisher's version ) (Closed access)Johanson-Blizzard syndrome (OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, multiple malformations such as nasal wing aplasia, and frequent mental retardation. We mapped the disease-associated locus to chromosome 15q14-21.1 and identified mutations, mostly truncating ones, in the gene UBR1 in 12 unrelated families with Johanson-Blizzard syndrome. UBR1 encodes one of at least four functionally overlapping E3 ubiquitin ligases of the N-end rule pathway, a conserved proteolytic system whose substrates include proteins with destabilizing N-terminal residues. Pancreas of individuals with Johanson-Blizzard syndrome did not express UBR1 and had intrauterine-onset destructive pancreatitis. In addition, we found that Ubr1(-/-) mice, whose previously reported phenotypes include reduced weight and behavioral abnormalities, had an exocrine pancreatic insufficiency, with impaired stimulus-secretion coupling and increased susceptibility to pancreatic injury. Our findings indicate that deficiency of UBR1 perturbs the pancreas' acinar cells and other organs, presumably owing to metabolic stabilization of specific substrates of the N-end rule pathway