Specific association of missense mutations in <i>CRELD1</i> with cardiac atrioventricular septal defects in heterotaxy syndrome

Zhian, Samaneh; Belmont, John W.; Maslen, Cheryl L.

doi:10.1002/ajmg.a.35457

Cited by 15 publications

(12 citation statements)

References 12 publications

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“…20 For example, CRELD1 gene mutations alter an amino acid at the N-linked glycosylation site, resulting in impaired glycosylation and abnormal protein folding. 15 Follow-up screening in 138 unaffected controls resulted in the identification of a similar duplication in one control subject. All three heterotaxy cases and the one control subject with the 4q25 duplication were noted to have Hispanic mothers.…”

Section: Discussionmentioning

confidence: 99%

Novel copy-number variants in a population-based investigation of classic heterotaxy

Rigler

Kay

Sicko

et al. 2015

Genetics in Medicine

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Purpose Heterotaxy is a clinically and genetically heterogeneous disorder. We investigated whether screening cases restricted to a classic phenotype would result in the discovery of novel, potentially causal copy-number variants. Methods We identified 77 cases of classic heterotaxy from all live births in New York State during 1998–2005. DNA extracted from each infant’s newborn dried blood spot was genotyped with a microarray containing 2.5 million single-nucleotide polymorphisms. Copy-number variants were identified with PennCNV and cnvPartition software. Candidates were selected for follow-up if they were absent in unaffected controls, contained 10 or more consecutive probes, and had minimal overlap with variants published in the Database of Genomic Variants. Results We identified 20 rare copy-number variants including a deletion of BMP2, which has been linked to laterality disorders in mice but not previously reported in humans. We also identified a large, terminal deletion of 10q and a microdeletion at 1q23.1 involving the MNDA gene; both are rare variants suspected to be associated with heterotaxy. Conclusion Our findings implicate rare copy-number variants in classic heterotaxy and highlight several candidate gene regions for further investigation. We also demonstrate the efficacy of copy-number variant genotyping in blood spots using microarrays.

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Section: Discussionmentioning

confidence: 99%

Novel copy-number variants in a population-based investigation of classic heterotaxy

Rigler

Kay

Sicko

et al. 2015

Genetics in Medicine

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“…To date, neither of both genes has been linked to cardiovascular development. CRELD1, encoding a member of a subfamily of epidermal growth factor-related proteins, has been proven to be crucial in cardiac development, and mutations in this gene have been reported to cause atrioventricular septal defect related to 3p deletion [Robinson et al, 2003;Kusuma et al, 2011;Zhian et al, 2012]. Thus, the CRELD1 gene deletion probably plays a causative role in the cardiac phenotype of atrial septal defect found in our patient as no other genes in the region have been implicated with CHD.…”

Section: B)mentioning

confidence: 66%

“…However, CRELD1 mutations were not observed in some 3p deletion patients with CHD (such as case q and r in table 1 ) and several patients without CHD carrying CRELD1 mutation [Shuib et al, 2009]. Analysis of more r(3) and 3p patients with and without CHD would be necessary for interpretation of non-penetrance and discovery of other risk factors that may interact with CRELD1 [Kusuma et al, 2011;Zhian et al, 2012].…”

Section: B)mentioning

confidence: 99%

Chromosome r(3)(p25.3q29) in a Patient with Developmental Delay and Congenital Heart Defects: A Case Report and a Brief Literature Review

Zhang

Song²,

Zhang³

et al. 2016

Cytogenet Genome Res

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Ring chromosome 3, r(3), is an extremely rare cytogenetic abnormality with clinical heterogeneity and only 12 cases reported in the literature. Here, we report a 1-year-old girl presenting distinctive facial features, developmental delay, and congenital heart defects with r(3) and a ∼10-Mb deletion of chromosome 3pterp25.3 (61,891-9,979,408) involving 42 known genes which was detected using G-banding karyotyping and CytoScan 750K-Array. The breakpoints in r(3) were mapped at 3p25.3 and 3q29. We also analyzed the available information on the clinical features of the reported cases with r(3) and 3p deletion syndrome in order to provide more valuable information of genotype-phenotype correlations. To our knowledge, this is the largest detected fragment described in r(3) cases and the second r(3) study using whole-genome microarray.

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“…(43). ” Nowadays, the overall epidemiological, experimental, and genetic data suggest that TGA, even in situs solitus, can be expression of laterality defects, as it has already been shown for some forms of CAVC (88–91). …”

Section: Resultsmentioning

confidence: 89%

Transposition of great arteries: new insights into the pathogenesis

et al. 2013

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Transposition of great arteries (TGA) is one of the most common and severe congenital heart diseases (CHD). It is also one of the most mysterious CHD because it has no precedent in phylogenetic and ontogenetic development, it does not represent an alternative physiological model of blood circulation and its etiology and morphogenesis are still largely unknown. However, recent epidemiologic, experimental, and genetic data suggest new insights into the pathogenesis. TGA is very rarely associated with the most frequent genetic syndromes, such as Turner, Noonan, Williams or Marfan syndromes, and in Down syndrome, it is virtually absent. The only genetic syndrome with a strong relation with TGA is Heterotaxy. In lateralization defects TGA is frequently associated with asplenia syndrome. Moreover, TGA is rather frequent in cases of isolated dextrocardia with situs solitus, showing link with defect of visceral situs. Nowadays, the most reliable method to induce TGA consists in treating pregnant mice with retinoic acid or with retinoic acid inhibitors. Following such treatment not only cases of TGA with d-ventricular loop have been registered, but also some cases of congenitally corrected transposition of great arteries (CCTGA). In another experiment, the embryos of mice treated with retinoic acid in day 6.5 presented Heterotaxy, suggesting a relationship among these morphologically different CHD. In humans, some families, beside TGA cases, present first-degree relatives with CCTGA. This data suggest that monogenic inheritance with a variable phenotypic expression could explain the familial aggregation of TGA and CCTGA. In some of these families we previously found multiple mutations in laterality genes including Nodal and ZIC3, confirming a pathogenetic relation between TGA and Heterotaxy. These overall data suggest to include TGA in the pathogenetic group of laterality defects instead of conotruncal abnormalities due to ectomesenchymal tissue migration.

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Specific association of missense mutations in CRELD1 with cardiac atrioventricular septal defects in heterotaxy syndrome

Cited by 15 publications

References 12 publications

Novel copy-number variants in a population-based investigation of classic heterotaxy

Novel copy-number variants in a population-based investigation of classic heterotaxy

Chromosome r(3)(p25.3q29) in a Patient with Developmental Delay and Congenital Heart Defects: A Case Report and a Brief Literature Review

Transposition of great arteries: new insights into the pathogenesis

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