Isolated bladder exstrophy associated with a de novo 0.9 Mb microduplication on chromosome 19p13.12

Draaken, Markus; Mughal, Sadaf S.; Pennimpede, Tracie; Wolter, Stefanie; Wittler, Lars; Ebert, Anne‐Karoline; Rösch, Wolfgang; Stein, Raimund; Bartels, Enrika; Schmidt, Dominik; Boemers, Thomas M.; Schmiedeke, Eberhard; Hoffmann, Per; Moebus, Susanne; Herrmann, Bernhard G.; Nöthen, Markus M.; Reutter, Heiko; Ludwig, Michael

doi:10.1002/bdra.23112

Cited by 20 publications

(18 citation statements)

References 32 publications

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“…Another array analysis of the DNA of 110 patients with bladder exstrophy identified 1 patient who carries a de novo microduplication on chromosome 19 [48]. This has not been described before.…”

Section: Bladder Exstrophymentioning

confidence: 76%

Genetic Aspects of Congenital Urologic Anomalies

Nordenskjöld

2015

European Urology Supplements

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Section: Bladder Exstrophymentioning

confidence: 76%

Genetic Aspects of Congenital Urologic Anomalies

Nordenskjöld

2015

European Urology Supplements

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“…Apart from sporadic cases, CBE is listed in association with 14 entities in the London Dysmorphology Database (LMD). Array CGH analysis has demonstrated an association between CBE and 22q11.21, 19p13.12 microduplications, while deletions in 3q and 1q have been reported in patients with OEIS complex [Kosaki et al, 2005;Draaken et al, 2010;Zaki et al, 2012;Draaken et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

Is 1p36 deletion associated with anterior body wall defects?

Çöllü

Yüksel

Sirin

et al. 2016

American J of Med Genetics Pt A

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Epispadias and exstrophy of the cloaca, also known as OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects), respectively constitute the most benign and severe ends of the bladder exstrophy-epispadias complex (BEEC) spectrum. In 2009, El-Hattab et al. reported the first patient with OEIS complex associated with a chromosome 1p36 deletion. Here we report a second patient with 1p36 deletion who also has classic bladder exstrophy, supporting the possible role of genes in this region in the development of BEEC. The absence of omphalocele and imperforate anus in our patient places him toward classic bladder exstrophy while presence of spina bifida and the absence of coccyx suggest an overlap with OEIS complex. An additional differential diagnosis is the pentalogy of Cantrell in our patient as he also has a diaphragmatic hernia and an incomplete sternum. This is the second observation of a ventral midline birth defect in association with 1p36 deletion syndrome, following El-Hattab et al.'s report [2009]. The three genes (NOCL2, DVL1, and MMP23B) discussed as possible candidates are also among the deleted ones in our patient, supporting the possible role of these genes in BEEC spectrum. © 2016 Wiley Periodicals, Inc.

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“…From studies both on chromosomal as well as base‐pair level several regions, genes and gene‐pathways have been suggested to be associated with BEEC susceptibility (Arkani et al, ; Baranowska Korberg et al, ; Draaken et al, ; Reutter et al, ; von Lowtzow et al, ). For example, a 900 kb microduplication on chromosome 19p13.12 was identified in one patient (Draaken et al, ). The duplication was confirmed de novo and one gene in the duplicated region, the Wiz gene, showed specific expression in cloaca and rectum regions in mice.…”

Section: Introductionmentioning

confidence: 99%

Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene

Lundin

Markljung

Körberg

et al. 2019

Molec Gen & Gen Med

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Background The bladder exstrophy‐epispadias complex (BEEC) is a congenital malformation of the bladder and urethra. The underlying causes of this malformation are still largely unknown; however, aside from environment, genetics is thought to play an essential role. The recurrent 22q11.2 microduplication is the most persistently detected genetic aberration found in BEEC cases. Methods We performed array comparative genomic hybridization (array‐CGH) analysis of 76 Swedish BEEC patients. Statistical analysis was performed on current dataset pooled with previously published data on the 22q11.2 microduplication in BEEC patients. We performed massive parallel sequencing (MPS) of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication followed by functional studies. Results We identified three additional cases with the 22q11.2 microduplication. Pooling data from this study with previously published reports showed a statistically significant enrichment of the 22q11.2 microduplication in BEEC patients (2.61% in cases vs. 0.08% in controls; OR = 32.6; p = 8.7 × 10−4). MPS of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication identified a novel variant in LZTR1 (p.Ser698Phe) in one patient. Functional evaluation of the LZTR1 p.Ser698Phe variant in live NIH 3T3 cells showed that the concentration and cytoplasmic mobility differ between the Lztr1wt and Lztr1mut, indicating a potential functional effect of the LZTR1mut. Conclusion Our study further emphasizes the involvement of the 22q11.2 region in BEEC development and highlights LZTR1 as a candidate gene underlying the urogenital malformation.

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Isolated bladder exstrophy associated with a de novo 0.9 Mb microduplication on chromosome 19p13.12

Cited by 20 publications

References 32 publications

Genetic Aspects of Congenital Urologic Anomalies

Genetic Aspects of Congenital Urologic Anomalies

Is 1p36 deletion associated with anterior body wall defects?

Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene

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