Holoprosencephaly and low molecular weight proteinuria: the human homologue of murine megalin deficiency.
We encountered a child with holoprosencephaly, pulmonary insufficiency, absent circulating vitamin D metabolites, mild albuminuria, and urinary excretion of vitamin D-binding protein. The child displayed a phenotype highly reminiscent of that observed in mice genetically deficient for megalin, a member of the low-density lipoprotein receptor superfamily. Only the Guthrie card was available from the child; the DNA sufficed for a limited haplotype analysis. We were not able to implicate the megalin gene locus directly; however, the possibility of a functional megalin defect in this child remains. To the best of our knowledge, this patient represents the first report that pathologic abnormalities consistent with megalin deficiency are present in humans.
Children's Hospital, University of Kiel, Humboldt University of Berlin, Germany.
D
D
Müller
T
T
Ankermann
U
U
Stephani
M
M
Kirschstein
T
T
Szelestei
F C
FC
Luft
T E
TE
Willnow
D000818:Animals; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D026541:Heymann Nephritis Antigenic Complex; D016142:Holoprosencephaly / Q000235:genetics* / Q000652:urine*; D006801:Humans; D007231:Infant, Newborn; D007678:Kidney Glomerulus / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D008970:Molecular Weight; D011507:Proteinuria / Q000175:diagnosis*; D012131:Respiratory Insufficiency / Q000175:diagnosis / Q000235:genetics
D005819:Genetic Markers; D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D004247:DNA