*143400 MULTICYSTIC RENAL DYSPLASIA, BILATERAL;
MRD
Alternative
titles; symbols
PELVIURETERIC JUNCTION OBSTRUCTION; PUJO
HYDRONEPHROSIS DUE TO PUJO
table OF
CONTENTS
Gene Map Locus: 6p
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TEXT
Cannon (1954)
described a curious family in which 5 males in 3
successive generations had unilateral
hydronephrosis. MacKay
(1945) observed congenital megaloureters with
hydronephrosis in 3 sibs (bilateral in 2). Two
other sibs were said to have died of congenital
sarcoma of the kidney. The paternal grandfather
died of pyonephrosis. The father died of cerebral
hemorrhage at 56. Jewell and
Buchert (1962) observed 4 cases in 3
generations. Aaron and
Robbins (1948) found hydronephrosis without
hydroureters and aberrant renal vessels possibly
responsible for obstruction at the ureteropelvic
junction in sibs. Simpson
and German (1970) described 7 families with
multiple cases of urinary tract anomalies, most of
them a form of obstructive uropathy, and reviewed
the literature on cases in sibs, twins, and other
relatives. McCormack et al.
(1981) reported congenital hydronephrosis in
father and son, with possible abnormality in
earlier generations.
In linkage analysis of 5 families with
hereditary pelviureteric junction (PUJO), Izquierdo
et al. (1992) found linkage to HLA. Maximal lod
scores were 3.090 at a recombination fraction of
0.1 with full penetrance, and 2.486 at a
recombination fraction of 0.1 with a penetrance of
90%. Use of the HOMOG program suggested genetic
heterogeneity with one locus on 6p in 4 of the
families and a different locus in 1 family. After
exclusion of the unlinked family, 2-point analysis
gave a maximal lod score of 3.9 at a recombination
fraction of 0.05 with full penetrance, and 4.2 at a
recombination fraction of 0.0 with 90% penetrance.
A further suggestion of a 6p locus for
hydronephrosis was provided by the observation of
Fryns et al. (1993): they
performed prenatal diagnosis on a 26-year-old
primigravida after the detection of oligohydramnios
with bilateral multicystic renal dysplasia on
routine echographic examination at 20 weeks'
gestation. Chromosomal analysis of the amniotic
fluid cell cultures demonstrated translocation
t(6;19)(p23.1;q13.4). Examination of the fetus
demonstrated bilateral multicystic renal dysplasia
with bilateral PUJ obstruction resulting in massive
hydronephrosis. Except for external morphologic
stigmata and severe lung hypoplasia secondary to
the oligohydramnios, no additional malformations
were noted. Groenen et al.
(1996) stated that an associated von
Mayer-Rokitansky-Kuster disorder (277000)
was found. Furthermore, the location of the
breakpoints in this translocation were revised to
6p21 and 19q13.1.
To elucidate the relationship between the
t(6;19) translocation and hereditary
hydronephrosis, Groenen et
al. (1996) carried out a molecular
characterization of a chromosome 19 cosmid clone
previously identified as spanning the translocation
in the index case. In a fragment straddling the
translocation breakpoint, they demonstrated DNA
sequences with a high degree of similarity to the
USF2 gene (600390)
that encodes the transcription factor upstream
stimulator factor 2. The chromosome 19 breakpoint
in the patient with bilateral multicystic renal
dysplasia appeared to have occurred in intron 7 of
the USF2 gene. Northern blot analysis of a variety
of human tissues revealed that the USF2 gene is
ubiquitously expressed. Furthermore, Northern blot
and 3-prime RACE analysis of mRNA isolated from
lung fibroblasts of the MRD patient failed to
detect a fusion transcript involving USF2
sequences, suggesting gene disruption rather than
the generation of a fusion gene as a possible
underlying mechanism. Groenen
et al. (1998) determined that the chromosome 6
breakpoint in this patient resides in intron 9 of
the CDC5L gene (602868).
Raffle (1955)
described a family in which 4 members in 2
generations had hydronephrosis. McHale
et al. (1996) gave an update on this family,
which was shown to contain 9 affected individuals
in 3 generations, and excluded linkage to HLA,
providing further evidence of genetic heterogeneity
in hereditary hydronephrosis. Mackintosh
et al. (1989) had also reported a large
'unlinked' family.
Mackintosh et al.
(1989) found linkage between familial
vesicoureteral reflux (193000)
and HLA, suggesting that this disorder may be
determined by mutation at the same locus on 6p as
multicystic renal dysplasia. Robson et al.
(1994, 1995)
proposed that multicystic dysplasia of the kidneys,
ureteropelvic junction obstruction, and
vesicoureteral reflux may have a common genetic
cause.
Santava et al. (1997)
studied 4 families with probable autosomal dominant
inheritance of congenital hydronephrosis caused by
ureteropelvic junction stenosis. In 2 of the
families, studies failed to show close linkage to
chromosome 6 markers; in the other 2, the findings
were consistent with linkage. HLA class I antigen
studies were done in all 4 families and class II
(HLA-DR; 142860)
antigen studies in 3. Male-to-male transmission was
observed in 2 of the families.
-
SEE ALSO
- Grosse et al.
(1973)
REFERENCES
- 1. Aaron, G.;
Robbins, M. A. :
- Hydronephrosis due to aberrant
vessels: remarkable familial incidence with
report of cases. J. Urol. 60:
702-705, 1948.
- 2. Cannon, J. F.
:
- Hereditary unilateral
hydronephrosis. Ann. Intern.
Med. 41: 1054-1060, 1954.
- 3. Fryns, J. P.;
Kleczkowska, A.; Moerman, P.; Vandenberghe, K.
:
- Hereditary hydronephrosis and the
short arm of chromosome 6. (Letter)
Hum. Genet. 91: 514-515, 1993.
PubMed ID : 8357406
- 4. Groenen, P. M.
A.; Garcia, E.; Debeer, P.; Devriendt, K.;
Fryns, J. P.; Van de Ven, W. J. M. :
- Structure, sequence, and chromosome
19 localization of human USF2 and its
rearrangement in a patient with multicystic
renal dysplasia. Genomics 38:
141-148, 1996.
PubMed ID : 8954795
- 5. Groenen, P. M.
A.; Garcia, E.; Thoelen, R.; Aly, M.;
Schoenmakers, E. F. P. M.; Devriendt, K.; Fryns,
J. P.; Van de Ven, W. J. M. :
- Isolation of cosmids corresponding
to the chromosome breakpoints of a de novo
autosomal translocation, t(6;19)(p21;q13.1), in
a patient with multicystic renal
dysplasia. Cytogenet. Cell
Genet. 75: 210-215, 1996.
PubMed ID : 9067426
- 6. Groenen, P. M.
A.; Vanderlinden, G.; Devriendt, K.; Fryns,
J.-P; Van de Ven, W. J. M. :
- Rearrangement of the human CDC5L
gene by a t(6;19)(p21;q13.1) in a patient with
multicystic renal dysplasia.
Genomics 49: 218-229, 1998.
PubMed ID : 9598309
- 7. Grosse, F. R.;
Kaveggia, L.; Opitz, J. M. :
- Familial hydronephrosis.
Z. Kinderheilk. 114: 313-322, 1973.
- 8. Izquierdo, L.;
Porteous, M.; Paramo, P. G.; Connor, J. M.
:
- Evidence for genetic heterogeneity
in hereditary hydronephrosis caused by
pelvi-ureteric junction obstruction, with one
locus assigned to chromosome 6p.
Hum. Genet. 89: 557-560, 1992.
PubMed ID : 1634233
- 9. Jewell, J. H.;
Buchert, W. I. :
- Unilateral hereditary
hydronephrosis: a report of four cases in three
consecutive generations. J.
Urol. 88: 129-136, 1962.
- 10. MacKay, H.
:
- Congenital bilateral megalo-ureters
with hydronephrosis. A remarkable family
history. Proc. Roy. Soc. Med.
38: 567-568, 1945.
- 11. Mackintosh, M.;
Almarhoos, G.; Heath, D. A. :
- HLA linkage with familial
vesicoureteral reflux and familial
pelvi-ureteric junction obstruction.
Tissue Antigens 34: 185-189, 1989.
PubMed ID : 2595723
- 12. McCormack, M.
K.; D'Aguillo, A.; Scully, J. :
- Autosomal dominant congenital
hydronephrosis (CH): prenatal diagnosis by
ultrasound. (Abstract) Am. J. Med.
Genet. 33: 85A only, 1981.
- 13. McHale, D.;
Porteous, M. E. M.; Wentzel, J.; Burn, J. :
- Further evidence of genetic
heterogeneity in hereditary
hydronephrosis. Clin. Genet.
50: 491-493, 1996.
PubMed ID : 9147880
- 14. Raffle, R. B.
:
- Familial hydronephrosis.
Brit. Med. J. 1: 580-582, 1955.
- 15. Robson, W. L.
M.; Rogers, R. C.; Leung, A. K. C. :
- MCDK, UPJO, and VUR: a common
genetic cause. (Letter) Am. J. Med.
Genet. 59: 398 only, 1995.
- 16. Robson, W. L.
M.; Rogers, R. C.; Leung, A. K. C. :
- Renal agenesis, multicystic
dysplasia, and uretero-pelvic junction
obstruction--a common pathogenesis?
(Letter) Am. J. Med. Genet.
53: 302 only, 1994.
PubMed ID : 7856668
- 17. Santava, A.;
Utikalova, A.; Bartova, A.; Drabek, J.; Santavy,
J.; Scheinar, J. :
- Familial hydronephrosis unlinked to
the HLA complex. Am. J. Med.
Genet. 70: 118-120, 1997.
PubMed ID : 9128928
- 18. Simpson, J. L.;
German, J. :
- Familial urinary tract anomalies.
(Letter) J.A.M.A. 212: 2264
only, 1970.
PubMed ID : 5467948
CLINICAL
SYNOPSIS
View
Clinical Synopsis Entry
CONTRIBUTORS
Carol A. Bocchini - updated : 8/6/1998
Victor A. McKusick - updated : 5/27/1997
Victor A. McKusick - updated : 4/28/1997
Victor A. McKusick - updated : 3/12/1997
Victor A. McKusick - updated : 3/6/1997
CREATION DATE
Victor A. McKusick : 6/4/1986
EDIT HISTORY
terry : 8/11/1998terry : 8/6/1998carol :
8/6/1998mark : 6/5/1997jenny : 6/5/1997terry :
5/27/1997alopez : 5/13/1997alopez : 5/13/1997alopez
: 4/28/1997terry : 3/12/1997terry : 3/6/1997mark :
3/6/1997terry : 3/6/1997terry : 12/26/1996mimadm :
9/24/1994carol : 8/18/1993carol : 9/18/1992supermim
: 3/16/1992supermim : 3/20/1990ddp : 10/27/1989
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