Familial ureteral abnormalities syndrome: genomic mapping, clinical findings

Byline: LuAnn Klemme (1), Alfred J. Fish (1), Stephen Rich (2), Beryl Greenberg (4), Beverly Senske (4), Miriam Segall (2) Keywords: Key words: Linkage analysis; Hydronephrosis; Hydroureter; Vesicoureteral reflux; Inherited ureteral defects; Chromosome 6p Abstract: Abnormal development of the ureter during embryogenesis, when occurring in multiple family members, appears to be a genetically determined defect with autosomal dominant inheritance and high penetrance, which can lead to significant kidney damage, renal failure, and death. We have studied 48 individuals within a large kindred in which ureteral-related abnormalities (including vesicoureteral reflux, ureteropelvic junction obstruction, duplicated ureters, and medullary sponge kidney) were segregated. Family members who had not had previous diagnostic studies were evaluated for presence or absence of ureteral abnormalities and we attempted to map the locus for this familial ureteral abnormalities syndrome (FUAS). These studies identified 11 asymptomatic individuals, previously assumed to be unaffected, with minor abnormalities. When linkage analysis between the inheritance of ureteral abnormalities and six marker loci glyoxalase I (GLO-1), major histocompatibility antigens (HLA-A, B, and DR/DQ), D6S288, and factor XIII antigen (F13A1) on the short arm of chromosome 6 was performed, the lod scores significantly rejected linkage over a 77.1-cM distance. These findings are in contrast to previous data suggesting linkage between the presence of ureteral abnormalities and HLA, and indicate the possibility of genetic heterogeneity of FUAS. Author Affiliation: (1) Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA, US (2) Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA, US (3) The Institute of Human Genetics, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA, US (4) Clinical Research Center, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA, US Article note: Received April 29, 1997 received in revised form September 15, 1997 accepted September 22, 1997