Trisomy 13 syndrome and neural tube defects

Rodrı́guez, José Ignacio; García, M.; Morales, Carmen; Morillo, Ana; Delicado, Alicia

doi:10.1002/ajmg.1320360429

Cited by 26 publications

(15 citation statements)

References 19 publications

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“…This implies that NTDs arise when a single copy of the critical region is present and that neural development is sensitive to the dosage of the gene (or genes) in the critical region. This conclusion is supported by the observation that NTDs also occur in trisomy 13 [Moerman et al, 1988;Rodriguez et al, 1990;Kalien et al, 1998]. …”

Section: Discussionmentioning

confidence: 74%

Neural tube defects and the 13q deletion syndrome: Evidence for a critical region in 13q33-34

Luo¹,

Balkin²,

Stewart³

et al. 2000

Am. J. Med. Genet.

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Neural tube defects (NTD) are common findings in the 13q deletion syndrome, but the relationship between the 13q- syndrome and NTDs is poorly understood. We present a child with a 13q deletion and lumbosacral myelomeningocele. This was a boy with microcephaly, telecanthus, minor facial anomalies, and ambiguous genitalia. Cytogenetic and fluorescence in situ hybridization analysis showed a de novo 46,XY,del(13)(q33.2-->qter) with no visible translocation. By using microsatellite markers, the deletion breakpoint was mapped to a 350-kb region between D13S274 and D13S1311 and was paternal in origin. An analysis of 13q deletions with NTDs, including the present case, suggests that a deletion in 13q33-34 is sufficient to cause an NTD. The deletions associated with NTDs are distal to and nonoverlapping with the previously defined critical region in 13q32 for the major malformation syndrome [Brown et al., 1999: Am J Hum Genet 57: 859-866]. Our analysis also suggests that one or more genes in 13q33-34 produces NTDs by haploinsufficiency.

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Section: Discussionmentioning

confidence: 74%

Neural tube defects and the 13q deletion syndrome: Evidence for a critical region in 13q33-34

Luo¹,

Balkin²,

Stewart³

et al. 2000

Am. J. Med. Genet.

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“…Association of NTDs with aneuploidy has been well documented in the literature [23,24,25,26]. Since NTDs usually occur as the result of multifactorial inheritance rather than secondary to a chromosomal disorder [14,15], some investigators considered that routine prenatal chromosome analysis was not warranted, particularly if apparently isolated defects [27].…”

Section: Discussionmentioning

confidence: 99%

Neural Tube Defects: The Experience of the Registry of Congenital Malformations of Alsace, France, 1995-2009

et al. 2014

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Context and Objective: Considering the lack of accurate and up-to-date information available about neural tube defects (NTDs) in France, the purpose of this study was to review clinical and epidemiological data of NTDs and to evaluate the current efficiency of prenatal diagnosis in Alsace (northeastern France). Methods: A population-based retrospective study was performed from data of the Registry of Congenital Malformations of Alsace between 1995 and 2009. Data were analyzed as a whole and according to the anatomical type of the malformation (anencephaly, cephalocele and spina bifida). Statistical analyses were carried out using the Statistical Package for the Social Sciences. Results: 272 NTDs were recorded divided in 113 cases of anencephaly (42%), 35 cases of cephalocele (13%) and 124 cases of spina bifida (45%). The total prevalence at birth of 14/10,000 (95% CI 13-16) was stable throughout the reporting period. A chromosome abnormality was identified in 27 cases (12% of all karyotyped cases). NTDs were prenatally diagnosed by ultrasound in 88% of the cases. The mean age upon prenatal diagnosis slightly declined during the 15-year period, significantly for spina bifida only. The global rate of terminations of pregnancy following prenatal diagnosis was 97% (230/238). Conclusion: This work constitutes a unique population-based study providing accurate and specific up-to-date data from a unique center over a longer period (1995-2009). The most important information concerns the high and stable prevalence, which calls into question the efficiency of the primary prevention by folic acid supplementation and the efficiency of prenatal diagnosis.

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“…In five fetuses, CNV screening identified variants that were classified as pathogenic or likely pathogenic (7.6%). Both Trisomy 13 (Patau syndrome, MIM# 264480) and Trisomy 18 (Edwards syndrome) are known to cause NTDs (Flannery & Kahler, ) (Rodríguez, García, Morales, Morillo, & Delicado, ). The 730 kb 22q11.2 deletion observed in fetus P315‐07 with myelomeningocele overlaps partly with the recurrent 3 Mb deletion associated with DiGeorge syndrome (MIM# 188400).…”

Section: Discussionmentioning

confidence: 99%

Targeted copy number screening highlights an intragenic deletion of WDR63 as the likely cause of human occipital encephalocele and abnormal CNS development in zebrafish

et al. 2018

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Congenital malformations affecting the neural tube can present as isolated malformations or occur in association with other developmental abnormalities and syndromes. Using high-resolution copy number screening in 66 fetuses with neural tube defects, we identified six fetuses with likely pathogenic mutations, three aneuploidies (one trisomy 13 and two trisomy 18) and three deletions previously reported in NTDs (one 22q11.2 deletion and two 1p36 deletions) corresponding to 9% of the cohort. In addition, we identified five rare deletions and two duplications of uncertain significance including a rare intragenic heterozygous in-frame WDR63 deletion in a fetus with occipital encephalocele. Whole genome sequencing verified the deletion and excluded known pathogenic variants. The deletion spans exons 14-17 resulting in the expression of a protein missing the third and fourth WD-repeat domains. These findings were supported by CRISPR/Cas9-mediated somatic deletions in zebrafish. Injection of two different sgRNA-pairs targeting relevant intronic regions resulted in a deletion mimicking the human deletion and a concomitant increase of abnormal embryos with body and brain malformations (41%, n = 161 and 62%, n = 224, respectively), including a sac-like brain protrusion (7% and 9%, P < 0.01). Similar results were seen with overexpression of RNA encoding the deleted variant in zebrafish (total abnormal; 46%, n = 255, P < 0.001) compared with the overexpression of an equivalent amount of wild-type RNA (total abnormal; 3%, n = 177). We predict the in-frame WDR63 deletion to result in a dominant negative or gain-of-function form of WDR63. These are the first findings supporting a role for WDR63 in encephalocele formation.

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Trisomy 13 syndrome and neural tube defects

Cited by 26 publications

References 19 publications

Neural tube defects and the 13q deletion syndrome: Evidence for a critical region in 13q33-34

Neural tube defects and the 13q deletion syndrome: Evidence for a critical region in 13q33-34

Neural Tube Defects: The Experience of the Registry of Congenital Malformations of Alsace, France, 1995-2009

Targeted copy number screening highlights an intragenic deletion of WDR63 as the likely cause of human occipital encephalocele and abnormal CNS development in zebrafish

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