PubMed HealthSearch

PubMed · 10076879

VACTERL as primary, polytopic developmental field defects.

Abstract

Previously we proposed that the VACTERL association represents a dysmorphogenetic response of the primary developmental field, i.e., polytopic developmental field defects (DFD). As such, it should conform to the essential attributes of a DFD, namely, heterogeneity, homology, and phylogeneity. To study its heterogeneity, we analyzed the data of the Spanish Collaborative Study of Congenital Malformations (ECEMC). Our results confirm the observations indicating that the different patterns of defects that constitute this entity are not only clinically variable but also causally heterogeneous. This causal heterogeneity, which is of crucial importance in defining developmental fields, gives additional credence to the hypothesis that VACTERL constitutes a primary polytopic DFD.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M L Martínez-Frías, J L Frías. 1999-03-05. VACTERL as primary, polytopic developmental field defects.. https://doi.org/10.1002/(sici)1096-8628(19990305)83%3A1%3C13%3A%3Aaid-ajmg4%3E3.3.co%3B2-o

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Heart, brain, and body wall defects in mice lacking calreticulin.

Calreticulin is a ubiquitously expressed protein, which has been implicated in a large number of cellular functions, including calcium storage and signaling, protein folding, and cell attachment. To examine the role of calreticulin during in vivo development, mice deficient in calreticulin were generated by targeted inactivation of the calreticulin gene. Calreticulin-deficient mutants die in utero, mostly in late gestation. Half of these embryos had decreased cardiac cell mass, associated with increased apoptosis of cardiac myocytes. In vitro differentiation cultures of calreticulin-deficient embryonic stem cells resulted in fewer embryoid bodies with contractile activity than cultures derived from calreticulin +/- stem cells (P < 0.001). Sixteen percent of the mutants exhibited exencephaly secondary to a defect in neural tube closure. Embryos surviving until Embryonic Day 16.5 had omphalocele. Lack of calreticulin did not influence survival of embryonic fibroblasts under various endoplasmic reticulum stress conditions. However, calreticulin did influence cell migration in a calcium- and substrate-dependent manner. We conclude that calreticulin is not essential during the early stages of embryonic development, but is important for the development of heart and brain and for ventral body wall closure. The observed abnormalities are compatible with a role of calreticulin in the modulation of cellular calcium signaling.

Abnormalities, Multiple

Terminal osseous dysplasia with pigmentary defects maps to human chromosome Xq27.3-xqter.

We have identified a four-generation family with 10 affected females manifesting one or more of the following features: osseous dysplasia involving the metacarpals, metatarsals, and phalanges leading to brachydactyly, camptodactyly, and other digital deformities; pigmentary defects on the face and scalp; and multiple frenula. There were no affected males. We performed X-inactivation studies on seven affected females, using a methylation assay at the androgen receptor locus; all seven demonstrated preferential inactivation of their maternal chromosomes carrying the mutation, and two unaffected females showed a random pattern. These findings indicate that this disorder is linked to the X chromosome. To map the gene for this disorder, we analyzed DNA from nine affected females and five unaffected individuals, using 40 polymorphic markers evenly distributed throughout the X chromosome. Two-point and multipoint linkage analyses using informative markers excluded most of the X chromosome and demonstrated linkage to a region on the long arm between DXS548 and Xqter. A maximum LOD score of 3.16 at recombination fraction 0 was obtained for five markers mapping to Xq27.3-Xq28. The mapping data should facilitate the identification of the molecular basis of this disorder.

Abnormalities, Multiple

Manitoba aboriginal kindred with original cerebro-oculo- facio-skeletal syndrome has a mutation in the Cockayne syndrome group B (CSB) gene.

Cerebro-oculo-facio-skeletal (COFS) syndrome is a rapidly progressive neurological disorder leading to brain atrophy with calcification, cataracts, microcornea, optic atrophy, progressive joint contractures, and growth failure. Cockayne syndrome (CS) is a recessively inherited neurodegenerative disorder characterized by low-to-normal birth weight; growth failure; brain dysmyelination with calcium deposits; cutaneous photosensitivity; pigmentary retinopathy, cataracts, or both; and sensorineural hearing loss. CS cells are hypersensitive to UV radiation because of impaired nucleotide excision repair of UV radiation-induced damage in actively transcribed DNA. The abnormalities in CS are associated with mutations in the CSA or CSB genes. In this report, we present evidence that two probands related to the Manitoba Aboriginal population group within which COFS syndrome was originally reported have cellular phenotypes indistinguishable from those in CS cells. The identical mutation was detected in the CSB gene from both children with COFS syndrome and in both parents of one of the patients. This mutation was also detected in three other patients with COFS syndrome from the Manitoba Aboriginal population group. These results suggest that CS and COFS syndrome share a common pathogenesis.

Abnormalities, Multiple