An unusual case of pediatric shortness of breath—questions

Abstract

BackgroundFraser syndrome (FS) features renal agenesis and cystic kidneys. Mutations of FRAS1 (Fraser syndrome 1) and FREM2 (FRAS1-related extracellular matrix protein 2) cause FS. They code for basement membrane proteins expressed in metanephric epithelia where they mediate epithelial/mesenchymal signalling. Little is known about whether and where these molecules are expressed in more mature kidneys.MethodsIn healthy and congenital polycystic kidney (cpk) mouse kidneys we sought Frem2 expression using a LacZ reporter gene and quantified Fras family transcripts. Fras1 immunohistochemistry was undertaken in cystic kidneys from cpk mice and PCK (Pkhd1 mutant) rats (models of autosomal recessive polycystic kidney disease) and in wild-type metanephroi rendered cystic by dexamethasone.ResultsNascent nephrons transiently expressed Frem2 in both tubule and podocyte epithelia. Maturing and adult collecting ducts also expressed Frem2. Frem2 was expressed in cpk cystic epithelia although Frem2 haploinsufficiency did not significantly modify cystogenesis in vivo. Fras1 transcripts were significantly upregulated, and Frem3 downregulated, in polycystic kidneys versus the non-cystic kidneys of littermates. Fras1 was immunodetected in cpk, PCK and dexamethasone-induced cyst epithelia.ConclusionsThese descriptive results are consistent with the hypothesis that Fras family molecules play diverse roles in kidney epithelia. In future, this should be tested by conditional deletion of FS genes in nephron segments and collecting ducts.

Anomalous Origin of Left Coronary Artery From Right Pulmonary Artery in Association With Scimitar Syndrome

“…Fraser syndrome is a multisystem malformation usually consisting of cryptophthalmos, syndactyly, and variable renal defects but is rarely associated with congenital heart defects. The present case is the first to report an association between the FRAS1 mutation with scimitar syndrome and ALCAPA ( 8 ).…”

Refinement of the HIVAN1 Susceptibility Locus on Chr. 3A1-A3 via Generation of Sub-Congenic Strains

“…Three positional candidates have been implicated in kidney disease. Frem2 is expressed in adult glomeruli, collecting ducts and transiently expressed in nascent nephrons (tubule and podocyte epithelia) [ 28 ]. FREM2 is required for maintenance of the integrity of the skin epithelium in utero , for renal development and for the maintenance of renal epithelial structure in adult mice [ 19 ].…”

“…Mutations in the human ortholog cause Fraser syndrome, which features renal agenesis and cystic, dysplastic or hypoplastic kidneys. Although Frem2 haploinsufficiency does not overtly affect nephrogenesis in mice, expression of Frem2 in adult kidneys correlated with cyst formation in homozygous mutant mice, indicating that the gene is required for maintaining the differentiated state of renal epithelia [ 28 ]. The CAST strain harbors multiple linked non-synonymous variants in Frem2 , and this gene is also differentially expressed in the congenic mouse kidney.…”

Multidisciplinary teams, and parents, negotiating common ground in shared-care of children with long-term conditions: A mixed methods study

“…A body of evidence is emerging about a positive relationship between MDT support and clinical outcomes [15,16] although this does not include qualitative studies to help interpret these results within the context of MDT/parent interactions. Our study contributes to this evidence-base by producing new insights into the way parents and MDTs embark on shared caring.…”

“…Few existing data relate to MDT management of childhood CKD, although a retrospective case-note review of 44 American children with renal insufficiency demonstrated better clinical outcomes for those managed in an MDT clinic compared to a general nephrology clinic, and multidisciplinary care was reported to improve outcomes of Canadian children with CKD [15,16]. However, interactions between MDTs and parents as they negotiate their respective roles when sharing children’s clinical care have received little research attention.…”