Pericentric inversion with partial 7(q35-->qter) duplication and 7pter deletion: diagnosis by cytogenetic and fish analysis in a 29-year-old male patient

We report on a 29-year-old male patient with an inverted 7(q35-qter) duplication diagnosed by combining cytogenetic and FISH studies. Traditional G-banding detected an abnormally long chromosome 7 which was further demonstrated to be entirely of chromosome 7 origin by using fluorescent whole chromosome 7 painting. The presence within the additional segment of a signal for 7q36 region (Williams control probe) and the absence of signals for 7q33 (Y938G5 probe) and 7q34 (Y815G5 probe) regions indicated that the breakpoint for this rearrangement was distal to 7q34 and proximal to 7q36. A distal 7p22 deletion was confirmed by the absence of signal for the 7p subtelomeric probe. Apart from kyphosis, developmental/mental retardation and abnormal ears, the clinical features of the present patient, who is the oldest individual ever reported with this duplication/deletion, were not typical for partial 7q trisomy syndrome. A review of the cases reported with 7(q35-qter) duplication is made and shows important clinical variability but constantly normal pre- and postnatal growth, a feature which can therefore be confirmed as distinctive of distal 7q trisomy syndrome.     

Missense mutation and hexanucleotide duplication in the PAX2 gene in two unrelated families with renal-coloboma syndrome (MIM 120330)

We present a family with autosomal-dominant inheritance of renal insufficiency caused by renal hypoplasia in six individuals. In all affected individuals, signs of optic disk dysplasia were detected, but most patients were asymptomatic. A heterozygous missense mutation in the PAX2 gene causing a Gly75 to Ser substitution was present in all affected individuals. A second, unrelated patient presented with ocular complaints related to optic disk dysplasia, and had a history of vesico-ureteral reflux. A heterozygous hexanucleotide duplication in the PAX2 gene was detected leading to the duplication of GluThr at positions 74 and 75. The mutations in these two families are the first mutations in the PAX2 gene that do not lead to a truncated protein. Mechanistically, these mutations are expected to result in abnormal folding of the PAX2 protein. These observations further expand the spectrum of clinical features associated with PAX2 mutations, and suggest that a distinct genetic disorder can be identified in patients with renal dysplasia through a careful eye examination. As the ocular manifestations in this syndrome are variable anomalies of retinal and optic disk dysplasia, we prefer the term “papillo-renal syndrome”. Received: 29 January 1998 / Accepted: 25 March 1998     

Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region for autistic disorder

Fine mapping of deletion regions in autistic patients represents a valuable screening tool for identifying candidate genes for autism. A number of studies have ascertained associations between autism and terminal 2q deletion with the breakpoint within 2q37. Here we describe a 12-year-old female patient with terminal 2q37.3 cryptic deletion and autistic behaviour. Her clinical features included hypotonia and feeding difficulties during infancy, coarse face with notably prominent forehead, prominent eyebrows, broad flat nasal bridge and round cheeks, small hands and feet with bilateral brachymetaphalangism, proximal implantation of the thumbs and short toenails, mild mental retardation and autistic behaviour. Recorded autistic features included early lack of eye contact and, during infancy, little social interactions, propensity to be stereotypically busy and to get anxious. In order to more closely delineate the linkage region for autism within 2q37, the findings in this patient were combined to those in 2 previously reported siblings with a well documented 2q37.3 deletion, but without autistic disorder. The exact size of the deleted segment was determined by mapping the deleted region in each group with a series of specific BAC clones linearly ordered on the 2q37 region. The deletion in the autistic patient appeared to be larger [breakpoint flanked by more centromeric clones RP11-680016 (236.9 Mb) and 201F21 (237.4 Mb)] than in the non autistic siblings [more telomeric clones RP11-205L13 (237.8 Mb) and 346114 (238.2 Mb)], revealing a distance of maximum 1.3 Mb between the breakpoints. Accordingly, the extent of the candidate region for susceptibility genes for autism on distal 2q is reduced to maximum 1.3 Mb. Comparison with another well documented autistic patient from the literature results in the same conclusion. These findings represent thus a further step towards identifying genes predisposing to autism.     

Bilateral autogenous breast reconstruction using perforator free flaps: a single center's experience

The authors present a single center's experience in bilateral breast reconstruction using perforator free flaps. The aim of this study was to show their indications, surgical technique, and results. A series of 53 patients underwent this procedure between February of 1996 and October of 2002. The surgical procedures were performed on patients with bilateral breast cancer (11 patients), patients with unilateral breast cancer and contralateral prophylactic mastectomy (22 patients), patients who had undergone bilateral prophylactic mastectomy (18 patients), a patient with Poland's syndrome, and a patient whose aesthetic breast augmentation had failed. Primary and secondary bilateral breast reconstructions were done in 18 and four patients, respectively. Eighteen patients who had earlier undergone breast reconstruction with implants had a tertiary breast reconstruction. Combined reconstruction (primary with secondary and primary with tertiary reconstruction) was done in 13 patients. Ninety-eight deep inferior epigastric perforator flaps and eight superior gluteal artery perforator flaps were used. The average operative time was 10 hours (range, 8 to 14.5 hours) for the simultaneous bilateral reconstruction. Total flap necrosis occurred in two cases (one deep inferior epigastric perforator flap and one superior gluteal artery perforator flap). Partial flap necrosis was not encountered, and fat necrosis was found in one deep inferior epigastric perforator flap (1 percent). Two pulmonary infections, one deep vein thrombosis, and one cardiac arrhythmia occurred as postoperative complications. The mean hospital stay was 9 days (range, 6 to 20 days). Abdominal bulging was reported in one patient. There were no recurrent disease or cancer manifestations, with an average follow-up of 3.5 years. This series clearly shows that perforator flaps are reliable and useful tools for bilateral breast reconstruction. This technique decreases the donor-site morbidity and offers an excellent aesthetic and long-term outcome and high patient satisfaction.     

Bacterial community composition in Lake Tanganyika: vertical and horizontal heterogeneity

Vertical and latitudinal differences in bacterial community composition (BCC) in Lake Tanganyika were studied during the dry season of 2002 by means of denaturing gradient gel electrophoresis analysis of PCR-amplified 16S RNA fragments. Dominant bands were sequenced and identified as members of the Cyanobacteria, Actinobacteria, Nitrospirae, green nonsulfur bacteria, and Firmicutes divisions and the Gamma- and Deltaproteobacteria subdivisions. The BCC in the lake displayed both vertical and latitudinal variation. Vertical changes in BCC were related to the thermal water column stratification, which influences oxygen and nutrient concentrations. Latitudinal variation was related to upwelling of deep water and increased primary production in the south of the lake. The number of bands per sample increased with bacterial production in the epilimnion of the lake, suggesting a positive diversity-productivity relationship.     

Specificity and reversibility of the transpeptidation reaction catalyzed by the Streptomyces R61 D-Ala-D-Ala peptidase

The specificity of the Streptomyces R61 penicillin-sensitive D-Ala-D-Ala peptidase has been re-examined with the help of synthetic substrates. The products of the transpeptidation reactions obtained with Gly-L-Xaa dipeptides as acceptor substrates are themselves poor substrates of the enzyme. This is in apparent contradiction with the classically accepted specificity rules for D-Ala-D-Ala peptidases. The Gly-L-Xaa dipeptide is regenerated by both the hydrolysis and transpeptidation reactions. The latter reaction is observed when another Gly-L-Xaa peptide or D-Alanine are supplied as acceptors. Utilization of substrates in which the terminal -COO(-) group has been esterified or amidated shows that a free carboxylate is not an absolute prerequisite for activity. The results are discussed in the context of the expected reversibility of the transpeptidation reaction.     

Trophic interactions within the microbial food web in a tropical floodplain lake (Laguna Bufeos, Bolivia)

Whether the primary role of bacterioplankton is to act as "remineralizers" of nutrients or as direct nutritional source for higher trophic levels will depend on factors controlling their production and abundance. In tropical lakes, low nutrient concentration is probably the main factor limiting bacterial growth, while grazing by microzooplankton is generally assumed to be the main loss factor for bacteria. Bottom-up and top-down regulation of microbial abundance was studied in six nutrient limitation and dilution gradient-size fractionation in situ experiments. Bacteria, heterotrophic nanoflagellates (HNF), ciliates and rotifers showed relatively low densities. Predation losses of HNF and ciliates accounted for a major part of their daily production, suggesting a top-down regulation of protistan populations by rotifers. Phosphorus was found to be strongly limiting for bacterial growth, whereas no response to enrichment with Nitrogen or DOC was detected. HNF were the major grazers on bacteria (g-0.43 d(-1)), the grazing coefficient increased when ciliates were added (g- 0.80 d(-1)) but decreased when rotifers were added (g- 0.23 d(-1)) probably due to nutrient recycling or top-down control of HNF and ciliates by rotifers.     

Control of planar cell polarity by interaction of DWnt4 and four-jointed

The Drosophila eye and the wing display specific planar cell polarity. Although Frizzled (Fz) signaling has been implicated in the establishment of ommatidial and wing hair polarity, evidence for the Wnt gene function has been limited. Here we examined the function of a Drosophila homolog of Wnt4 (DWnt4) in the control of planar polarity. We show that DWnt4 mRNA and protein are preferentially expressed in the ventral region of eye disc. DWnt4 mutant eyes show polarity reversals mostly in the ventral domain, consistent with the ventral expression of DWnt4. Ectopic expression of DWnt4 in the dorsoventral (DV) polar margins is insufficient to induce ommatidial polarity but becomes inductive when coexpressed with Four-jointed (Fj). Similarly, DWnt4 and Fj result in synergistic induction of hair polarity toward the source of expression in the wing. Consistent with genetic interaction, we provide evidence for direct interaction of DWnt4 and Fj transmembrane protein. The extracellular domain of Fj is required for direct binding to DWnt4 and for the induction of hair polarity. In contrast to the synergy between DWnt4 and Fj, DWnt4 antagonizes the polarizing effect of Fz. Our results suggest that DWnt4 is involved in ommatidial polarity signaling in the ventral region of the eye and its function is mediated by interacting with Fj.     

Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.