We describe a newborn boy with multiple anomalies, including bilateral split foot and an interstitial deletion of chromosome 2 (q24.2-q31.1). Four additional cases in 2 families involving similar deletions have been reported. Bilateral digital anomalies of hands and feet were seen in all 5 cases, including a wide cleft between the first and second toes, wide halluces, brachysyndactyly of the toes, and camptodactyly of the fingers. Other common manifestations have included postnatal growth and mental retardation, microcephaly, down-slanting palpebral fissures, micrognathia, and apparently low-set ears. Bilateral digital anomalies were reported in 22 of 24 cases with deletions including at least part of region 2q24-q31. Digital anomalies were not prevalent in 18 patients with deletions of chromosome 2q not overlapping 2q24-q31. 2q31.1 appears to be the common deleted segment in all cases with significant digital anomalies, which implies the existence of one or more genes involved in distal limb morphogenesis in this region. HOXD13 and EVX2, located in the proximity of 2q31, were not deleted in our patient by Southern analysis. Bilateral digital malformations of the hands and feet associated with other anomalies should be evaluated by chromosome analysis focused at the 2q24-q31 region.

The retinal pigment epithelium (RPE) of the eye expresses an abundant 61 kDa protein (RPE65), that is developmentally regulated and tissue-specific. In our efforts toward understanding the specialized functions and development of the RPE, and the origins of inherited retinal degenerations, we have characterized the human gene encoding the 61 kDa protein. This is the first structural characterization of a gene transcribed specifically in the RPE. The gene maps to human chromosome 1p31. The sequence encoding the transcript spans over 20 kb, and is interrupted by 13 introns. A putative transcription start site lies 54 bp upstream of the initiation codon. A single transcript of approximately 2.9 kb is present in human RPE, and is not detected in other tissues. The deduced 533 amino acid sequence of the human protein is 98.7% identical to the bovine, but shows no significant similarity to any other entry in the databases. Expression of the 61 kDa protein appears to depend on the presence of environmental cues, since the corresponding transcripts are rapidly lost from RPE cells established in culture. Down regulation may occur post-transcriptionally, since AU-rich elements proposed to target RNA for rapid degradation are present throughout the 3'-untranslated region. The tissue-specific expression, high abundance, evolutionary conservation, developmental regulation, and sequence of the 3'-untranslated region suggest that the 61 kDa protein is the product of a functionally important gene whose expression is tightly regulated.

The nuclear-cytoplasmic shuttling heterogeneous nuclear RNA-binding protein (hnRNP) Squid (Sqd) is required during Drosophila melanogaster oogenesis, where it plays a critical role in the regulation of the TGFalpha-like molecule Gurken (Grk). Three Sqd isoforms have been described, SqdA, S and B, and two of these, SqdA and SqdS, differentially function in grk mRNA nuclear export, cytoplasmic transport and translational control during oogenesis. Here, we report that Sqd is also required for the regulation of oskar (osk) mRNA, functioning in the cytoplasmic localization of the osk transcript. In oocytes from sqd females, osk mRNA is not efficiently localized to the posterior pole, but rather accumulates at the anterior cortex. Furthermore, anterior patterning defects observed in embryos from sqd females expressing only the SqdS protein isoform suggest that Sqd may also play a role in the translational regulation of the mislocalized osk mRNA. These findings provide additional support for models of mRNA regulation in which cytoplasmic events, such as localization and translational regulation, are coupled. These results also place Sqd among an emerging class of proteins, including such other members as Bruno (Bru) and Hrb27C/Hrp48, which function in multiple aspects of both grk and osk mRNA regulation during Drosophila oogenesis.

We report on 2 girls with terminal deletion of the short arm of chromosome 9 with concurrent duplication unrecognizable by routine chromosome studies. The phenotype of the patients was not specifically suggestive of the 9p-syndrome in the absence of trigonocephaly and long philtrum as cardinal manifestations. In addition to psychomotor retardation, their manifestations were mild and include upward slant of palpebral fissures and dolichomesophalangy which are characteristic of del(9p). Chromosome abnormalities were de novo in both cases. The two rearranged chromosomes 9 exhibit similar G-banding patterns and suggested the possible duplication of distal 7p. Fluorescence in situ hybridization (FISH) with a chromosome-7 specific library probe indeed identified that one derivative chromosome 9 was the result of a translocation between chromosomes 7 and 9 [der(9)t(7;9)(p15.3;p24] but failed to detect a signal on the other derivative 9. In the second case, the concurrent abnormality was an inverted duplication of proximal 9p and deletion of distal 9p [inv dup(9)(p13-->p22::p22-->qter)] confirmed by FISH using a chromosome 9 specific library probe. FISH clearly identified the origin of these 2 abnormal chromosomes 9 and provided crucial information for clinical evaluation. We emphasize the importance of utilizing updated cytogenetic and molecular techniques in the precise delineation of subtle or complex abnormalities where there are no useful phenotypic clues.

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