Genetics of Congenital Anomalies

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Genetics".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 4349

Special Issue Editor


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Guest Editor
1. Division of Neonatology and Pediatric Intensive Care (H.R.), Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander University Nürnberg-Erlangen, Erlangen, Germany
2. Institute of Human Genetics, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany
Interests: molecular genetics; DNA; PCR; DNA sequencing; gene expression; cloning; animal models; zebrafish; developmental genetics; human genetics
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Special Issue Information

Dear Colleagues,

Congenital anomalies are the major cause of embryonic and foetal death across European populations. Moreover, congenital anomalies represent the major single cause of infant mortality, childhood morbidity, and long-term disability in Europe. In Europe, congenital anomalies affect around 50,000 newborns per annum (incidence 1:15 livebirths). Each year, around 25% of all paediatric deaths, and around 33% of all paediatric hospital admissions, are associated with anomalies.

Approximately 10% of all congenital anomalies are monogenic, in approx. 5% chromosomal defects are causally present, in approx. 5% existing maternal diseases are possible causes of anomalies, 20% are polygenic multifactorial diseases, and for the remaining 60% of anomalies, the causes are still unclear.

This Special Issue will focus on the emerging role of genetic factors in the expression of human congenital anomalies 

Prof. Dr. Heiko Reutter
Guest Editor

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Keywords

  • congenital anomalies
  • molecular genetics
  • exome sequencing
  • developmental biology
  • functional characterization

Published Papers (2 papers)

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12 pages, 1255 KiB  
Article
Exome Survey and Candidate Gene Re-Sequencing Identifies Novel Exstrophy Candidate Genes and Implicates LZTR1 in Disease Formation
by Ricarda Köllges, Jil Stegmann, Sophia Schneider, Lea Waffenschmidt, Julia Fazaal, Katinka Breuer, Alina C. Hilger, Gabriel C. Dworschak, Enrico Mingardo, Wolfgang Rösch, Aybike Hofmann, Claudia Neissner, Anne-Karolin Ebert, Raimund Stein, Nina Younsi, Karin Hirsch-Koch, Eberhard Schmiedeke, Nadine Zwink, Ekkehart Jenetzky, Holger Thiele, Kerstin U. Ludwig and Heiko Reutteradd Show full author list remove Hide full author list
Biomolecules 2023, 13(7), 1117; https://doi.org/10.3390/biom13071117 - 13 Jul 2023
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Abstract
Background: The bladder exstrophy-epispadias complex (BEEC) is a spectrum of congenital abnormalities that involves the abdominal wall, the bony pelvis, the urinary tract, the external genitalia, and, in severe cases, the gastrointestinal tract as well. Methods: Herein, we performed an exome analysis of [...] Read more.
Background: The bladder exstrophy-epispadias complex (BEEC) is a spectrum of congenital abnormalities that involves the abdominal wall, the bony pelvis, the urinary tract, the external genitalia, and, in severe cases, the gastrointestinal tract as well. Methods: Herein, we performed an exome analysis of case-parent trios with cloacal exstrophy (CE), the most severe form of the BEEC. Furthermore, we surveyed the exome of a sib-pair presenting with classic bladder exstrophy (CBE) and epispadias (E) only. Moreover, we performed large-scale re-sequencing of CBE individuals for novel candidate genes that were derived from the current exome analysis, as well as for previously reported candidate genes within the CBE phenocritical region, 22q11.2. Results: The exome survey in the CE case-parent trios identified two candidate genes harboring de novo variants (NR1H2, GKAP1), four candidate genes with autosomal-recessive biallelic variants (AKR1B10, CLSTN3, NDST4, PLEKHB1) and one candidate gene with suggestive uniparental disomy (SVEP1). However, re-sequencing did not identify any additional variant carriers in these candidate genes. Analysis of the affected sib-pair revealed no candidate gene. Re-sequencing of the genes within the 22q11.2 CBE phenocritical region identified two highly conserved frameshift variants that led to early termination in two independent CBE males, in LZTR1 (c.978_985del, p.Ser327fster6) and in SLC7A4 (c.1087delC, p.Arg363fster68). Conclusions: According to previous studies, our study further implicates LZTR1 in CBE formation. Exome analysis-derived candidate genes from CE individuals may not represent a frequent indicator for other BEEC phenotypes and warrant molecular analysis before their involvement in disease formation can be assumed. Full article
(This article belongs to the Special Issue Genetics of Congenital Anomalies)
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11 pages, 2592 KiB  
Article
Pathophysiological Role of Variants of the Promoter Region of CITED2 Gene in Sporadic Tetralogy of Fallot Patients with Cellular Function Verification
by Zhuo Chen, Huan-Xin Chen, Hai-Tao Hou, Xiu-Yun Yin, Qin Yang and Guo-Wei He
Biomolecules 2022, 12(11), 1644; https://doi.org/10.3390/biom12111644 - 7 Nov 2022
Cited by 3 | Viewed by 1677
Abstract
Tetralogy of Fallot (TOF) is a common congenital heart malformation. Genetic variants in the CITED2 coding region are known to be significantly associated with cardiac malformation, but the role of variants in the CITED2 promoter region in the development of TOF remains unclear. [...] Read more.
Tetralogy of Fallot (TOF) is a common congenital heart malformation. Genetic variants in the CITED2 coding region are known to be significantly associated with cardiac malformation, but the role of variants in the CITED2 promoter region in the development of TOF remains unclear. In this study, we investigated CITED2 promoter variants in the DNA of 605 subjects, including 312 TOF patients and 293 unrelated healthy controls, by Sanger sequencing. We identified nine CITED2 gene promoter variants (including one novel heterozygous variant). Six were found only in patients with TOF and none in the control group. The transcriptional activity of the CITED2 gene promoter in mouse cardiomyocyte (HL-1) cells was significantly altered by the six variants (p < 0.05). The results of the electrophoretic mobility change assay and JASPAR database analysis showed that these variants generated or destroyed a series of possible transcription factor binding sites, resulting in changes in the CITED2 protein expression. We conclude that CITED2 promoter variants in TOF patients affect transcriptional activity and may be involved in the occurrence and progression of TOF. These findings may provide new insights into molecular pathogenesis and potential therapeutic insights in patients with TOF. Full article
(This article belongs to the Special Issue Genetics of Congenital Anomalies)
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