Gene locus ambiguity in posterior urethral valves/prune-belly syndrome

Abstract

Lower urinary tract obstruction by posterior urethral valves (PUV) is an important cause of congenital renal failure in male infants. Though population-based studies point to a role of genetic factors in the etiology of PUV, no clear evidence for a specific gene defect for PUV has been observed so far. Here we present a consanguineous family with four male descendants affected by PUV and a healthy girl, suggestive of autosomal recessive inheritance. One boy presented with prune-belly syndrome (PBS) in addition to PUV. Using a DNA chip-based genome-wide linkage analysis, we identified a region of homozygosity for the affected boys in an interval of 35 cM on chromosome 1q41-44 with a maximum multipoint LOD score of Z(max) = 3.134 at theta = 0 for single nucleotide polymorphisms (SNPs) rs158724-rs720163. By applying a second genetic model based on the assumption of a male-limited phenotype and the girl being carrier of the genetic defect without expressing the phenotype, a second alternative locus of 9 cM on chromosome 11p11 was identified with a LOD score of Z(max) = 3.61 at theta = 0. Equal significance for both loci with a LOD score of Z(max) = 3.01 at theta = 0 was obtained after the affection status of the female descendant was set "unknown". We suppose that most probably, only one of the two identified loci harbours the disease-causing gene. As the interpretation of the girl's status remains uncertain, we are not able to exclude one of the two loci. Analyses of additional informative families will be important to exclude one of the two loci and to restrict the critical interval.

Familial recurrence of urethral stenosis/atresia

“…By contrast, several cases of posterior urethral valves have been described in siblings and monozygotic or dizygotic twins (Schreuder et al, 2008). Sex-influenced recessive inheritance has been suggested in one report (Ramasamy et al, 2005) and autosomal recessive inheritance in another (Weber et al, 2005). In reviewing these cases, it is apparent that diagnoses were often reached by ultrasound examination and based upon the appearance of the dilated bladder and prostatic urethra.…”

Genetic Aspects of Congenital Urologic Anomalies

“…PUVs cause different degrees of urinary obstruction in males and even can result in end-stage renal failure. PUVs are usually isolated but can also be part of syndromes like the prune belly syndrome in association with hypoplasia of the abdominal wall and cryptorchidism [27]. There are some reports of chromosomal abnormalities, mainly involving chromosome 10 (ring chromosome and terminal q deletion) but one case with prune belly syndrome and a 6p25.3 micro deletion has also been found [28][29][30].…”

“…This supports a genetic background for PUVs. Furthermore, in one consanguineous family with four males born with PUV, a study using a DNA chip-based, genomewide linkage analysis identified two possible chromosomal loci on chromosomes 1 and 11 [27]. More families need to be identified for further studies to clarify the pathogenesis of PUVs.…”

Genetic Basis of Posterior Urethral Valves Inheritance

“…Some authors even reported recurrence in 3 to 5 siblings respectively(13,14). Though several reports describe cases of monozygotic twins from whom only on boy was affected, the probability that 5 consecutive brothers were affected from PUVs were 5000-8000 5 i.e.1:3,125E+18 -3,2768E+18 if genetic had no role.…”