The Wolf-Hirschhorn syndrome (WHS), is a well known contiguous gene syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical manifestations of the syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called "WHSCR-2" [Zollino et al., 2003].

In this study, we present evidence that neurogenic cells inhibit the differentiation of cardiogenic cells. When cells of the entire area pellucida at stage 5 were dissociated and reaggregated, the aggregates differentiated into neural tissues and other structures of any germ layer origin, except for heart tissues, despite the fact that the cardiogenic cells are already committed to differentiate. The phenomenon also occurs from stages 6 to 8, during which cells are in a higher state of commitment. Using combinations of different regions of the area pellucida, it was confirmed that neurogenic cells are responsible for the inhibition of cardiogenic cell differentiation. The inhibition is not species-specific because quail and chick neurogenic cells inhibit each other's cardiogenic cell differentiation. Direct contact between cardiogenic and neurogenic cells seems to be necessary for inhibition because cardiogenic cell differentiation takes place if cardiogenic and neurogenic cells are separated by a porous membrane. Dissociated neural tubes from early stages, but not dissociated telencephalon from 2-day-old chicks, also inhibit cardiogenic cell differentiation. These results suggest that neurogenic cells may sequester molecules necessary for the differentiation of cardiogenic cells rather than produce inhibitory molecules.

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The beta-amyloid precursor proteins (betaAPPs) are a family of glycosylated transmembrane proteins that include in their sequences the beta-amyloid peptide, a major component of the characteristic amyloid deposits or senile plaques found in the brains of Alzheimer's disease patients and aged Down's syndrome subjects. Various betaAPP isoforms, mainly betaAPP-695, betaAPP-714, betaAPP-751 and betaAPP-770, the number corresponding to the number of amino acids they encode, resulting from the alternative splicing of a single primary transcript have been described. Using oligonucleotides recognizing each of the four major Alzheimer's betaAPP mRNAs, we have found that each betaAPP mRNA displays a specific temporal and spatial pattern of expression. The prototype isoform betaAPP-695 occurs early in cells actively implicated in morphogenetic events, as those mesodermal cells invaginating at the level of the primitive streak, and it is later restricted to the neurectodermal (neural tube, neural crest and neurogenic placode) derivatives. By contrast, the longest isoform betaAPP-770 appears later and restricted to mesodermal and endodermal derivatives. The isoforms betaAPP-714 and betaAPP-751 are still expressed later than the other two isoforms and distributed ubiquitously, though betaAPP-714 transcripts predominate typically within the neural tube.