Copy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula

Brosens, Erwin; Marsch, Florian; Jong, Elisabeth M. de; Zaveri, Hitisha P.; Hilger, Alina C.; Choinitzki, Vera; Hölscher, A.; Hoffmann, Per; Herms, Stefan; Boemers, Thomas M.; Ure, Benno M.; Lacher, Martin; Ludwig, Michael; Eussen, Bert; Helm, Robert M. van der; Douben, Hannie; Opstal, Diane Van; Wijnen, René; Beverloo, H. Berna; Bever, Yolande van; Brooks, Alice S.; IJsselstijn, Hanneke; Scott, Daryl A.; Schumacher, Johannes; Tibboel, Dick; Reutter, Heiko; Klein, Annelies de

doi:10.1038/ejhg.2016.86

Cited by 29 publications

(30 citation statements)

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“…Furthermore, the herereported Patient 7 with anorectal malformation and esophagus anomalies inherited a microdeletion of chromosomal region 7q35 from her father. Of interest, this deletion shows complete physical overlap with the pathogenic de novo distal 7q deletion in a patient with "V, A, TE" presented by Brosens et al (2016) (Supporting Fig. S3).…”

Section: Discussionmentioning

confidence: 91%

“…The herereported patient 20 (McDonald-McGinn et al, 2015) presented with the recurrent 22q11.21 microdeletion and a VATER/VACTERL-like phenotype comprising an anorectal malformation and renal anomalies. Both, anorectal malformations and renal anomalies were repeatedly reported in patients with 22q11.2 microdeletion or microduplication syndrome (Worthington et al, 1997;Schramm et al, 2011;No€ el et al, 2014;Brosens et al, 2016). For the two microduplications published by Schramm et al (2011) andBrosens et al (2016) the exact physical size of the CNV was available.…”

Section: Discussionmentioning

confidence: 99%

“…Both, anorectal malformations and renal anomalies were repeatedly reported in patients with 22q11.2 microdeletion or microduplication syndrome (Worthington et al, 1997;Schramm et al, 2011;No€ el et al, 2014;Brosens et al, 2016). For the two microduplications published by Schramm et al (2011) andBrosens et al (2016) the exact physical size of the CNV was available. Comparison of the physical overlap of these two microduplications with the microdeletion found here, reveals a smallest region of overlap comprising amongst other genes TBX1 (see Supporting Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Although only a few large studies have been published, there are several lines of evidence that (de novo) CNVs are associated with the expression of structural birth defects, other than defects of the central nervous system (Southard et al, 2012;Hilger et al, 2013;Brosens et al, 2016). Depending on the investigated birth defect, de novo CNVs have been assumed to be causative in up to 20% of cases (Goldmuntz et al, 2011;Dworschak et al, 2015;Brosens et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

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Array‐based molecular karyotyping in 115 VATER/VACTERL and VATER/VACTERL‐like patients identifies disease‐causing copy number variations

Zhang

Marsch

Kause

et al. 2017

Birth Defects Research

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Array‐based molecular karyotyping in 115 VATER/VACTERL and VATER/VACTERL‐like patients identifies disease‐causing copy number variations

Zhang

Marsch

Kause

et al. 2017

Birth Defects Research

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“…ROH regions had to contain at least 50 probes and be larger than 1 Mb in size in line with established criteria (48,49). CNVs were profiled according to previously described prioritization methods (50). To determine the consanguinity coefficient (f) and the inbreeding coefficient (F), we used the genomic oligoarray and SNP-array evaluation tool v3.0 (51) and a 50 probes minimum for ROH region.…”

Section: Discussionmentioning

confidence: 99%

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Halim

Wilson

Oliver

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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106

108

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Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2 (ACTG2), a smooth muscle contractile gene. However, evidence suggesting a recessive origin of the disease also exists. Using combined homozygosity mapping and whole exome sequencing, a genetically isolated family was found to carry a premature termination codon in Leiomodin1 (LMOD1), a gene preferentially expressed in vascular and visceral smooth muscle cells. Parents heterozygous for the mutation exhibited no abnormalities, but a child homozygous for the premature termination codon displayed symptoms consistent with MMIHS. We used CRISPR-Cas9 (CRISPR-associated protein) genome editing of Lmod1 to generate a similar premature termination codon. Mice homozygous for the mutation showed loss of LMOD1 protein and pathology consistent with MMIHS, including late gestation expansion of the bladder, hydronephrosis, and rapid demise after parturition. Loss of LMOD1 resulted in a reduction of filamentous actin, elongated cytoskeletal dense bodies, and impaired intestinal smooth muscle contractility. These results define LMOD1 as a disease gene for MMIHS and suggest its role in establishing normal smooth muscle cytoskeletal–contractile coupling.

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Associated anomalies in cases with esophageal atresia

Stoll

Alembik

Dott

et al. 2017

American J of Med Genetics Pt A

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Esophageal atresia (EA) is a common type of congenital anomaly. The etiology of esophageal atresia is unclear and its pathogenesis is controversial. Infants with esophageal atresia often have other non-EA associated congenital anomalies. The purpose of this investigation was to assess the prevalence and the types of these associated anomalies in a defined population. The associated anomalies in cases with EA were collected in all livebirths, stillbirths, and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population-based registry of congenital malformations. Of the 116 cases with esophageal atresia, representing a prevalence of 2.99 per 10,000, 54 (46.6%) had associated anomalies. There were 9 (7.8%) cases with chromosomal abnormalities including 6 trisomies 18, and 20 (17.2%) nonchromosomal recognized dysmorphic conditions including 12 cases with VACTERL association and 2 cases with CHARGE syndrome. Twenty five (21.6%) of the cases had multiple congenital anomalies (MCA). Anomalies in the cardiovascular, the digestive, the urogenital, the musculoskeletal, and the central nervous systems were the most common other anomalies. The anomalies associated with esophageal atresia could be classified into a recognizable malformation syndrome or pattern in 29 out of 54 cases (53.7%). This study included special strengths: each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. In conclusion the overall prevalence of associated anomalies, which was close to one in two cases, emphasizes the need for a thorough investigation of cases with EA. A routine screening for other anomalies may be considered in infants and in fetuses with EA.

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Copy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula

Cited by 29 publications

References 50 publications

Array‐based molecular karyotyping in 115 VATER/VACTERL and VATER/VACTERL‐like patients identifies disease‐causing copy number variations

Array‐based molecular karyotyping in 115 VATER/VACTERL and VATER/VACTERL‐like patients identifies disease‐causing copy number variations

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Associated anomalies in cases with esophageal atresia

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