Mutations in theCOL4A4 and COL4A3 genes cause familial benign hematuria.
Familial benign hematuria (FBH) is a common autosomal dominant disorder characterized by the presence of persistent or recurrent hematuria. The clinical and pathologic features of this syndrome resemble those of early Alport syndrome (AS), and for this reason a common molecular defect has been proposed. The COL4A3/4 genes seem to be involved in both autosomal AS and FBH. This study involves a linkage analysis for the COL4A3/4 loci and a search for mutations within these genes in 11 biopsy-proven FBH families. Haplotype analysis showed that linkage to the COL4A3/4 locus could not be excluded in eight of nine families. One family was not linked to this locus; however, it included three affected women who could be X-linked AS carriers. Two families were too small to perform linkage analysis. COL4A3 and COL4A4 mutation screening disclosed six new pathogenic mutations, two in the COL4A3 gene (G985V and G1015E) and four in the COL4A4 gene (3222insA, IVS23-1G>C, 31del11, and G960R). It is the first time that mutations within the COL4A3 gene are described in families with FBH. This study clearly demonstrates the main role of the COL4A4 and COL4A3 genes in the pathogenesis of FBH.
Badenas
Cèlia
C
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.|*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Praga
Manuel
M
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Tazón
Bárbara
B
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.|*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Heidet
Laurence
L
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Arrondel
Christelle
C
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Armengol
Anna
A
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.|*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Andrés
Amado
A
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Morales
Enrique
E
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Camacho
Juan Antonio
JA
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Lens
Xose
X
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Dávila
Sonia
S
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Milà
Montse
M
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Antignac
Corinne
C
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Darnell
Alejandro
A
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Torra
Roser
R
*Nephrology and Genetics Departments, Hospital Clínic, Barcelona, Spain; Nephrology Department, Hospital 12 de Octubre, Madrid, Spain; Nephrology Department, Inserm U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France; Hospital Sant Joan de Déu, Barcelona, Spain; and #Nephrology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D008040:Genetic Linkage; D006239:Haplotypes; D006417:Hematuria / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D011110:Polymorphism, Genetic