RT Journal Article
SR Electronic
T1 X-linked Alport Syndrome
JF Journal of the American Society of Nephrology
JO J. Am. Soc. Nephrol.
FD American Society of Nephrology
SP 649
OP 657
VO 11
IS 4
A1 JAIS, JEAN PHILIPPE
A1 KNEBELMANN, BERTRAND
A1 GIATRAS, IANNIS
A1 MARCHI, MARIO DE
A1 RIZZONI, GIANFRANCO
A1 RENIERI, ALESSANDRA
A1 WEBER, MANFRED
A1 GROSS, OLIVER
A1 NETZER, KAI-OLAF
A1 FLINTER, FRANCES
A1 PIRSON, YVES
A1 VERELLEN, CHRISTINE
A1 WIESLANDER, JÖRGEN
A1 PERSSON, ULF
A1 TRYGGVASON, KARL
A1 MARTIN, PAULA
A1 HERTZ, JENS MICHAEL
A1 SCHRÖDER, CORNELIS
A1 SANAK, MAREK
A1 KREJCOVA, SARKA
A1 CARVALHO, MARIA FERNANDA
A1 SAUS, JUAN
A1 ANTIGNAC, CORINNE
A1 SMEETS, HUBERT
A1 GUBLER, MARIE CLAIRE
YR 2000
UL http://jasn.asnjournals.org/content/11/4/649.abstract
AB Abstract. Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease. Considerable allelic heterogeneity has been observed. A “European Community Alport Syndrome Concerted Action” has been established to delineate accurately the AS phenotype and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of the 401 male patients belonging to the 195 families with COL4A5 mutation are presented. All male patients were hematuric, and the rate of progression to end-stage renal failure and deafness was mutation-dependent. Large deletions, nonsense mutations, or small mutations changing the reading frame conferred to affected male patients a 90% probability of developing end-stage renal failure before 30 yr of age, whereas the same risk was of 50 and 70%, respectively, in patients with missense or splice site mutation. The risk of developing hearing loss before 30 yr of age was approximately 60% in patients with missense mutations, contrary to 90% for the other types of mutations. The natural history of X-linked AS and correlations with COL4A5 mutations have been established in a large cohort of male patients. These data could be used for further evaluation of therapeutic approaches.