Androgenetic/biparental mosaicism causes placental mesenchymal dysplasia.

BACKGROUND: Placental mesenchymal dysplasia (PMD) is a distinct syndrome of unknown aetiology that is associated with significant fetal morbidity and mortality. Intrauterine growth restriction is common, yet, paradoxically, many of the associated fetuses/newborns have been diagnosed with Beckwith-Wiedemann syndrome (BWS). METHODS: We report two cases of PMD with high levels of androgenetic (complete paternal uniparental isodisomy) cells in the placenta and document, in one case, a likely androgenetic contribution to the fetus as well. RESULTS: The same haploid paternal complement found in the androgenetic cells was present in coexisting biparental cells, suggesting origin from a single fertilisation event. CONCLUSIONS: Preferential allocation of the normal cells into the trophoblast explains the absence of trophoblast overgrowth, a key feature of this syndrome. Interestingly, the distribution of androgenetic cells appears to differ from that reported for artificially created androgenetic mouse chimeras. Androgenetic mosaicism for the first time provides an aetiology for PMD, and may be a novel mechanism for BWS and unexplained intrauterine growth restriction.

Localization of HuC (ELAVL3) to chromosome 19p13.2 by fluorescence in situ hybridization utilizing a novel tyramide labeling technique.

HuC is a neural-specific member of the Elav family of RNA-binding proteins. This highly conserved gene family plays a crucial role in neurogenesis, and HuC (HGMW-approved symbol ELAVL3) is expressed at an early stage of neural development. Using a novel tyramide fluorescence in situ hybridization (T-FISH) technique, we localized HuC to chromosome 19p13.2. This localization was confirmed by radiation hybrid mapping and coincides with that of HuR (HGMW-approved symbol ELAVL1), another elav family member. Dual T-FISH analysis with HuC and HuR probes, however, indicated distinct loci, with HuC being centromeric to HuR. This study demonstrates the utility of T-FISH in colocalizing two genes on the same chromosomal preparation using only biotinylated probes.

Localization of human elav-like neuronal protein 1 (Hel-N1) on chromosome 9p21 by chromosome microdissection polymerase chain reaction and fluorescence in situ hybridization.

Hel-N1 is a member of the highly conserved elav family of neuronal genes. It shares considerable sequence homology with HuD, another human member, and both genes are expressed in brain. HuD was recently mapped to chromosome 1p34. Here, we have utilized chromosome microdissection polymerase chain reaction and fluorescence in situ hybridization to map Hel-N1 to chromosome 9p21. The different chromosomal locations of these homologous genes underscore their distinct identities.

Assignment of the human heart tetrodotoxin-resistant voltage-gated Na+ channel alpha-subunit gene (SCN5A) to band 3p21.

The chromosomal location of SCN5A, the gene encoding the principal voltage-gated Na+ channel expressed in human heart, has been determined by three independent methodologies: somatic cell hybrid mapping, chromosomal microdissection-polymerase chain reaction, and fluorescence in situ hybridization. The SCN5A gene was assigned to the short arm of chromosome 3 (band 3p21) by all three approaches. These data are further evidence that striated muscle Na+ channel genes are dispersed in the genome.

Molecular and cytogenetic investigation of complex tissue-specific duplication and loss of chromosome 21 in a child with a monosomy 21 phenotype.

Several recent molecular studies have suggested that the clinical phenotype of Down syndrome may be due to triplication of 21q22 [McCormick et al., 1989] as initially suggested by Niebuhr [1974], and perhaps just 21q22.2 [Korenberg et al., 1989, 1990; Rahmani et al., 1989]. Recently, we studied a patient with a phenotype inconsistent with Down syndrome, whose lymphocyte karyotype on several occasions detected only 46,XX,-21, + dic(21)(qter----p11::p11----qter). Combined karyotype and molecular studies on both lymphocytes and fibroblasts allowed correct identification of the abnormality as a complex monosomy/trisomy 21 mosaicism involving a marker derived from idic (21) (p11), and probable assignment of a maternal origin for the error(s). The patient's phenotype was found to be most consistent with monosomy 21. Detailed study of our patient underscores (1) the need for confirmation that there is phenotype/karyotype correlation and (2) the usefulness of molecular analyses to complement the cytogenetic interpretation of marker chromosomes.