[Collagen type IV nephropathy: from thin basement membrane nephropathy to Alport syndrome].
BACKGROUND
Collagen type IV nephropathy includes the Goodpasture syndrome, thin basement membrane nephropathy and the Alport syndrome. Mutations in the coding Col(IV)A3/A4 and Col(IV)A5 genes are probable causes of the latter two. Thin basement membrane nephropathy is mostly familial and has an autosomal dominant inheritance, at least 40% of the families have hematuria that co-segregates with the Col(IV)A3 and/or Col(IV)A4 loci. 85% of Alport syndrome cases are transmitted as an X-linked semidominant form due to Col(IV)A5 mutations. About 14% of Alport syndrome cases exhibit autosomal recessive, and 1% autosomal dominant inheritance, both caused by mutations in the Col(IV)A3 or Col(IV)A4 genes in boys and in girls.


OBJECTIVE
The co-segregation pattern of hematuria was examined in two families with thin basement membrane nephropathy and one family with the Alport syndrome, using short tandem repeat markers, spanning the Col(IV)A3/A4 and Col(IV)A5 loci to assess their linkage to the clinical symptoms and morphological alterations in the renal biopsy specimens.


METHODS
Markers: Col(IV)A3: CAll and D2S401; Col(IV)A4: HaeIII/RFLP; and Col(IV)A5: DXS456, 2B6 and 2B20.


RESULTS
The hematuria displayed autosomal dominant inheritance and co-segregated with Col(IV)A3 markers in one of the thin basement membrane nephropathy families. In the second, the hematuria did not segregate with the Col(IV)A3/A4 or Col(IV)A5 loci, suggesting the possibility of another genetic locus for the disease. The Alport syndrome exhibited autosomal recessive inheritance and did not link to Col(IV)A5 markers, and the Col(IV)A3/A4 markers were informative only in part.


CONCLUSIONS
Knowledge of the inheritance and genetic background of collagen type IV nephropathy will be very important in the diagnostics and genetic counseling in the future.
Szegedi Tudományegyetem, Szent-Györgyi Albert Orvos es Gyógyszerésztudományi Centrum, Altalános Orvostudományi Kar, Gyermekgyógyászati Klinika es Gyermekegészségügyi Központ, Szeged. endreffy@pedia.szote.u-szeged.hu
Emoke
E
Endreffy
Zoltán
Z
Ondrik
Eva
E
Kemény
Zoltán
Z
Vas
Zoltán
Z
Maróti
Gerda
G
Lencse
Csaba
C
Bereczki
Ibolya
I
Haszon
Sándor
S
Túri
Béla
B
Iványi
D000293:Adolescent; D000328:Adult; D019867:Anti-Glomerular Basement Membrane Disease / Q000235:genetics* / Q000473:pathology; D024141:Collagen Type IV / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D050533:Glomerular Basement Membrane / Q000473:pathology; D034381:Hearing Loss / Q000235:genetics; D006417:Hematuria / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008297:Male; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
D024141:Collagen Type IV; D005819:Genetic Markers