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EDITOR--Fragile X syndrome is the most common chromosomal cause of inherited mental retardation. At the chromosome level, this syndrome is characterised by the presence of a fragile site at Xq27.3. [...]

We report on three individuals of Muslim Arab origin from a village located in Northern Israel affected by an apparent autosomal recessive syndrome characterized by distinctive facial phenotype of which the most prominent feature is ocular hypertelorism. The other clinical features of the syndrome include variable degree of mental retardation, genital abnormalities dominated by short penis, and skeletal abnormalities including chest deformity combination of upper pectus carinatum with lower pectus excavatum, and short palms with broad short fingers. Affected individuals displayed distinctive facial features including upslanting palpebral fissures, thick eyebrows, long philtrum, wide mouth with thin upper lip and upturned corners of the mouth, widows peak, broad nasal bridge, and simple ears with fleshy overfolded helices. This phenotype does not fully meet typical diagnostic features of any known condition. © 2009 WileyLiss, Inc.

Robinow syndrome comprises dysmorphic facial features, short stature, brachymesomelia, segmental spine defects, and genital hypoplasia. The range of severity in this disorder is broad. We report on the clinical and molecular findings of two sib pairs from the same extended family with Robinow syndrome due to a novel intragenic ROR2deletion involving exons 6 and 7 that could not be detected by sequencing. The affected individuals exhibited variability with respect to the cleft lip, cleft palate, and cardiac findings and for the presence in one of the patients of syringomyelia, which has not been previously reported in Robinow syndrome. © 2008 WileyLiss, Inc.

Neurodegenerative disorders (ND) encompass clinically and genetically heterogeneous diseases with considerable overlap of their clinical, neuropathological and molecular phenotype. Various causes of neurodegeneration in disease may affect eventually the same proteins within protein networks. To identify common changes in ND, we compared brain protein changes detected by 2-D electrophoresis in four mouse models for ND:  (i) Parkinson's disease, (ii) Huntington's disease, (iii) prion disease Scrapie, and (iv) a model for impaired synaptic transmission. To determine specificity of these changes for ND, we extended the scope of our investigation to three neurological conditions that do not result in neurodegeneration (non-ND). We detected 12 to 216 consistent qualitative or quantitative protein changes in individual ND and non-ND models when compared to controls. Up to 36% of these proteins were found to be altered in multiple disease states (at least three) and were therefore termed nodal point proteins. Alterations in alpha B-Crystallin and splicing factor 3b (subunit 4) occurred in at least three ND but not in non-ND. In contrast, alterations in peroxiredoxin 1 and 3, astrocytic phosphoprotein PEA15, complexin 2 and aminoacylase 1 were common to both ND and non-ND. Finally, we investigated the expression pattern of the nodal point proteins in three inbred mouse strains and found different protein abundance (expression polymorphisms) in all cases. Nodal point proteins showing expression polymorphisms may be candidate proteins for disease associated modifiers.

Cherubism is a rare autosomal dominant fibro-osseous disorder that affects almost exclusively maxilla and mandible. Extracranial skeletal involvement is rare. We report on three affected males in three generations. The youngest affected relative was examined at age 4 months. He also had craniosynostosis. His affected father and grandfather had cherubism and clubbing of the fingers. Cherubism was mapped to region 4p16. Because of the associated craniosynostosis, we excluded the FGFR3 gene as a candidate gene for cherubism. Am. J. Med. Genet. 95:325–331, 2000. © 2000 Wiley-Liss, Inc.

Variations of turbulent mixing in the water column and in the benthic boundary layer were observed with a microstructure profiler in the Hudson River estuary during two cruises in summer and fall of 1995. Variability patterns of stratification, shear, Richardson number (Ri), and turbulent dissipation rates () were similar to those of earlier observations, with strong turbulence in the weakly stratified bottom layer, weak turbulence in the halocline during neap tides, and low Ri and high spanning the water column during spring ebbs. Depth-integrated turbulent dissipation rates ∫ ρ dzapproximately equaled the work done by the tidal pressure gradient force adjusted for the change in tidal kinetic energy. Alternatively, a suitable scaling for ∫ ρ dzis also provided by the product of bottom shear stress and depth-average velocity τb, a relationship that fails at slack tide, however. At heights above bottom of z 0.3 m, and again excepting slack tides, observed were highly correlated with a law-of-the-wall dissipation rate bu3∗/(κz). Ratios bwere close to 1. Here, the friction velocity is u∗, and von Kármán’s constant is κ.Most profiles of the normalized dissipation rate bshowed a weak increase with zin the lowest 1.5 m, a departure from law of the wall scaling attributed to stable stratification. Such deviations from the law of the wall were smallest during spring floods when the near-bottom stratification was weak or unstable. Turbulence in the stratified water column well above the bottom appeared to be locally generated by shear instability even though band were correlated throughout the water column. During spring ebbs, exceeded bby almost an order of magnitude at z 2 m.

Examines the tidal, fortnightly and longer-term variability of turbulent mixing within the uniform segment of a partially mixed estuary, the Hudson River. Largest vertical salt flux during spring ebbs; Consistent level of small-scale mixing with the integral momentum and salt budgets in the uniform segment of the river.

We report on two independent alterations of the NF1 gene in a three-generation kindred with neurofibromatosis type 1 (NF1). Using temperature gradient gel electrophoresis (TGGE) in a mutation analysis of exon 31 of the NF1 gene we detected the previously reported nonsense mutation R1947X. This C-to-T transition at codon 1947 in exon 31 is considered to represent a mutation `“ot spot” of the NF1 gene due to ^5mCpG deamination. All living family members together with their genomic DNA were included in this investigation. However, the mutation R1947X was absent from two undoubtedly affected siblings of the propositus. Another NF1 mutation (889-2A→G) was identified in the two sibs by the protein truncation test (PTT). The novel splice site mutation 889-2A→G results in a skip of NF1 exon 7 during splicing and protein truncation due to frameshift. The two NF1 alterations are linked to different paternal haplotypes. In our study of a three-generation kindred, R1947X represents a de novo mutation whereas 889-2A→G is an inherited splice mutation. Implications for phenotype variation are discussed. Am. J. Med. Genet. 83:6–12, 1999. © 1999 Wiley-Liss, Inc.

We screened a total of 92 unrelated patients with neurofibromatosis type 1 (NF1) for mutations in exon 37 of the NF1 gene, by using temperature gradient gel electrophoresis. Two novel mutations were found: a 4 bp deletion in a so-called quasi-symmetric element (6789delTTAC) and a recurrent nonsense mutation, which was identified in two unrelated patients, at codon 2264 (C6792A). The independent origin of the latter mutation in two families was confirmed by haplotype analysis. The nonsense mutation and the 4 bp deletion are both predicted to lead to a truncated protein product lacking the Cterminal 20% (aproximately) of its sequence. The occurrence of three independent mutations among 92 NF1 patients at codons 2263–2264 (exon 37) suggests that a specific search for mutations in this area should be undertaken in screening programs for NF1 mutations.