Author/Editor		Turco, Alberto E; Bresin, Elena; Rossetti, Sandro; Peterlin, Borut; Morandi, Raffaella; Pignati, Pier Franco
Title		Rapid DNA-based prenatal diagnosis by genetic linkage in three families with Alport's syndrome
Type		članek
Source		Am J Kidney Dis
Vol. and No.		Letnik 30, št. 2
Publication year		1997
Volume		str. 174-9
Language		eng
Abstract		Alport's syndrome (AS) is a clinically and genetically heterogeneous progressive inherited glomerulonephritis characterized by hematuria, sensorineural hearing loss, ocular lesions, and specific alterations of the glomerular basement membrane. Typically, AS shows an X-linked dominant pattern of inheritance, with mutations affecting the collagen type IV alpha5 chain gene (COL4A5) at Xq22. Rarely, AS is caused in some families by mutations of the COL4A3/A4 genes on chromosome 2q, showing an autosomal recessive transmission. Very few families have been described with possible autosomal dominant AS, but no mutations in any of the COL4 genes have been found. We describe three unrelated families affected with a severe AS phenotype in which DNA-based prenatal diagnosis by linkage analysis was made in fetuses at risk for the disease. In two families, the pedigree structure and the clinical picture were consistent with typical X-linked dominant AS. In these families, autosomal inheritance was also ruled out molecularly. In one family, despite careful clinical and molecular evaluation, the mode of transmission could not be firmly established. We used tightly linked and intragenic COL4A5 markers, as well as COL4A3/A4-linked markers. A chromosome Y-specific marker for fetal sex determination was simultaneously used. In all the families, before the fetal analysis, the putative at-risk X haplotype was identified with high diagnostic accuracy. We diagnosed a healthy male fetus in one family, and female but carrier fetuses in the other two kindreds, who decided not to terminate their pregnancies. We used rapid nonisotopic polymerase chain reactionbased methods, and the results were available within 2 do 3 days. The genetic significantly affected the reproductive decisions of the parents. (abstract truncated at 2000 characters.)
Descriptors		LINKAGE (GENETICS) DNA NEPHRITIS, HEREDITARY PRENATAL DIAGNOSIS AMNIOCENTESIS ADULT CHORIONIC VILLI SAMPLING GENETIC MARKERS GENOTYPE PEDIGREE POLYMERASE CHAIN REACTION