The broader phenotypic spectrum of congenital caudal abnormalities associated with mutations in the caudal type homeobox 2 gene

Autor: Marjon van Slegtenhorst, Paul Lasko, Jill R. Murrell, Romy van de Putte, Courtney Manning, Mary-Alice Abbott, Constance T. R. M. Stumpel, Jacqueline Leonard, Iris A.L.M. van Rooij, Servi J. C. Stevens, Han G. Brunner, Alexander Hoischen, Karin E. M. Diderich, Louise C. Pyle, Jorune Balciuniene
Přispěvatelé: MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Klinische Genetica, MUMC+: DA Klinische Genetica (5), Clinical Genetics
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Male
Pathology
medicine.medical_specialty
caudal regression syndrome
Genotype
SACRAL AGENESIS
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Biology
Sacral Agenesis
persistent cloaca
sirenomelia
Vertebral segmentation defect
homeobox gene
Exome Sequencing
VACTERL
Genetics
medicine
Humans
Abnormalities
Multiple
CDX2 Transcription Factor
Genetic Predisposition to Disease
imperforate anus
Genetic Testing
Child
CDX2
Alleles
Genetic Association Studies
Genetics (clinical)
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Caudal regression syndrome
ELONGATION
Sacrococcygeal Region
Infant
Newborn
Infant
medicine.disease
HOX
Phenotype
digestive system diseases
Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10]
Sirenomelia
Mutation
embryonic structures
Homeobox
GROWTH
Female
PARAHOX
Imperforate anus
Zdroj: Clinical Genetics, 101, 183-189
Clinical Genetics, 101, 2, pp. 183-189
Clinical Genetics, 101(2), 183-189. Wiley
Clinical Genetics, 101(2), 183-189. Wiley-Blackwell Publishing Ltd
ISSN: 0009-9163
DOI: 10.1111/cge.14076
Popis: Contains fulltext : 248942.pdf (Publisher’s version ) (Open Access) The caudal type homeobox 2 (CDX2) gene encodes a developmental regulator involved in caudal body patterning. Only three pathogenic variants in human CDX2 have been described, in patients with persistent cloaca, sirenomelia and/or renal and anogenital malformations. We identified five patients with de novo or inherited pathogenic variants in CDX2 with clinical phenotypes that partially overlap with previous cases, that is, imperforate anus and renal, urogenital and limb abnormalities. However, additional clinical features were seen including vertebral agenesis and we describe considerable phenotypic variability, even in unrelated patients with the same recurrent p.(Arg237His) variant. We propose CDX2 variants as rare genetic cause for a multiple congenital anomaly syndrome that can include features of caudal regression syndrome and VACTERL. A causative role is further substantiated by the relationship between CDX2 and other proteins encoded by genes that were previously linked to caudal abnormalities in humans, for example, TBXT (sacral agenesis and other vertebral segmentation defects) and CDX1 (anorectal malformations). Our findings confirm the essential role of CDX2 in caudal morphogenesis and formation of cloacal derivatives in humans, which to date has only been well characterized in animals.
Databáze: OpenAIRE
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