Bladder exstrophy and extreme genital anomaly in a patient with pure terminal 1q deletion: Expansion of phenotypic spectrum

Zaki, Maha S.; Gillessen‐Kaesbach, Gabriele; Vater, Inga; Caliebe, Amke; Siebert, Reiner; Kamel, Alaa K.; Mohamed, Amal M.; Mazen, Inas

doi:10.1016/j.ejmg.2011.09.003

Cited by 18 publications

(14 citation statements)

References 27 publications

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“…Moreover, the AgCC observed in patients with point mutations or small deletions altering mainly ZBTB18 is partial and characterized by a small splenium with the absence of beak (patients #Z1 and #Z4 and #2, #3 and #5 in Cohen et al 2016). However, complete or subtotal AgCC have been reported in patients with larger 1q deletions not included in our study (Boland et al 2007; Caliebe et al 2010; Hemming et al 2016; Zaki et al 2012), suggesting that one or more proximal genes on chromosome 1 could also lead or predispose to AgCC.…”

Section: Discussionmentioning

confidence: 69%

Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU

Nava²,

et al. 2017

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Subtelomeric 1q43q44 microdeletions cause a syndrome associating intellectual disability, microcephaly, seizures and anomalies of the corpus callosum. Despite several previous studies assessing genotype-phenotype correlations, the contribution of genes located in this region to the specific features of this syndrome remains uncertain. Among those, three genes, AKT3, HNRNPU and ZBTB18 are highly expressed in the brain and point mutations in these genes have been recently identified in children with neurodevelopmental phenotypes. In this study, we report the clinical and molecular data from 17 patients with 1q43q44 microdeletions, four with ZBTB18 mutations and seven with HNRNPU mutations, and review additional data from 37 previously published patients with 1q43q44 microdeletions. We compare clinical data of patients with 1q43q44 microdeletions with those of patients with point mutations in HNRNPU and ZBTB18 to assess the contribution of each gene as well as the possibility of epistasis between genes. Our study demonstrates that AKT3 haploinsufficiency is the main driver for microcephaly, whereas HNRNPU alteration mostly drives epilepsy and determines the degree of intellectual disability. ZBTB18 deletions or mutations are associated with variable corpus callosum anomalies with an incomplete penetrance. ZBTB18 may also contribute to microcephaly and HNRNPU to thin corpus callosum, but with a lower penetrance. Co-deletion of contiguous genes has additive effects. Our results confirm and refine the complex genotype-phenotype correlations existing in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of AKT3, ZBTB18 and HNRNPU in humans.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-017-1772-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 69%

Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU

Nava²,

et al. 2017

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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: 96%

“…CBE includes epispadias, wide pubic symphysis, and anteriorly displaced anus. It is considered as the most common component of the BEEC spectrum [Draaken et al, 2010;Lundin et al, 2010;Zaki et al, 2012]. The term "exstrophy" is the exact description, meaning "turned inside-out."…”

Section: Introductionmentioning

confidence: 98%

“…Exstrophy of the cloaca, also known as OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects) belongs to the severe end of the BEEC spectrum [Martinez-Frias et al, 2001;Zaki et al, 2012]. OEIS complex, has been reported in association with several syndromes and chromosomal abnormalities [KepplerNoreuil, 2001;Martinez-Frias et al, 2001;Hertzberg et al, 2003;Kosaki et al, 2005;Chen, 2007].…”

Section: Introductionmentioning

confidence: 99%

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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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“…In spite of this variation, these patients are collectively considered as the chromosome 1q43‐q44 deletion syndrome (OMIM: 612337). More recently, the use of new microarray, and molecular technology has resulted in genome coordinates that are more clearly defined, facilitating the establishment of more accurate correlations between the clinical manifestations and different haploinsufficient genes [van Bon et al, ; Perrone et al, ; Zaki et al, ]. However, many articles are focused on identifying the genes related with specific alterations (particularly abnormalities of the corpus callosum, microcephaly, seizures and autism), and do not include a thorough description of the whole clinical patterns [Orellana et al, ; Ballif et al, ; Nagamani et al, ; Perlman et al, ; Petersen et al, ].…”

Section: Introductionmentioning

confidence: 99%

Deletion 1q43‐44 in a patient with clinical diagnosis of Warburg–Micro syndrome

Arroyo-Carrera

Tristancho²,

Bermejo‐Sánchez

et al. 2015

American J of Med Genetics Pt A

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Warburg–Micro syndrome (WARBM) is an autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy and central nervous system malformations. This syndrome is caused by mutations in the RAB3GAP1/2 and RAB18 genes, part of the Rab family, and in the TBC1D20 gene, which contributes to lipid droplet formation/metabolism. Here we present a patient with clinical diagnosis of WARBM syndrome, who did not have mutations in either the RAB3GAP1/2 genes, in the main exons of RAB18, nor in the TBC1D20 gene. However, the analysis with CGH‐array detected a 9.6 Mb deletion at 1q43‐qter. We performed a genotype–phenotype correlation using 20 previously published patients in whom the coordinates of the deleted regions were defined. The comparative analysis revealed that the current patient and three of the other 20 patients share the loss of six genes, four of which are related with the family of G proteins, and are strongly expressed in the brain, retina, heart and kidney. Consequently, their haploinsufficiency may result in different combinations of clinical alterations, including some of those of WARBM syndrome. In addition, the haploinsufficiency of other genes may contribute to other defects and clinical variability. Additionally, for the genotype–phenotype correlation, one must also consider molecular pathways that can result in the observed alterations. To early confirm a genetic diagnosis is essential for the patient and family. The current patient was considered as having a recessive syndrome, but since he had a “de novo” deletion, there was not an increased recurrence risk. © 2015 Wiley Periodicals, Inc.

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Bladder exstrophy and extreme genital anomaly in a patient with pure terminal 1q deletion: Expansion of phenotypic spectrum

Cited by 18 publications

References 27 publications

Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU

Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU

Is 1p36 deletion associated with anterior body wall defects?

Deletion 1q43‐44 in a patient with clinical diagnosis of Warburg–Micro syndrome

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