Split hand/foot malformation (SHFM) or ectrodactyly is a rare genetic condition affecting limb development. SHFM shows clinical and genetic heterogeneity. It can present as an isolated form or in combination with additional anomalies affecting the long bones (nonsyndromic form) or other organ systems including the craniofacial, genitourinary and ectodermal structures (syndromic ectrodactyly). This study reports a girl with SHFM who also exhibited developmental delay, mild dysmorphic facial features and sensorineural hearing loss. High-resolution banding analysis indicated an interstitial deletion within the 7q21 band. FISH using locus-specific BAC probes confirmed the microdeletion of 7q21.3. Chromosomal microarray analysis also revealed a microdeletion of 1.856 Mb in 7q21.3. However, a larger 8.44-Mb deletion involving bands 7q21.11q21.2 was observed, and the breakpoints were refined. The phenotype and the candidate genes underlying the pathogenesis of this disorder are discussed.

Clinical suspicion is vital for early detection of PWS. Confirmation of the diagnosis requires complex multi-tier molecular genetic testing.

The genetic analysis of monogenic disorders has over the past 3 decades resulted in the identification of thousands of genes which either cause or impact these conditions; most of these disorders have no therapies. The modulation of the transcripts and proteins encoded by these genes might be anticipated to have therapeutic utility, either by their upregulation (e.g. of mutated recessive disease genes encoding proteins with residual enzymatic activity, of genes that are sequentially similar to, and that functionally recapitulate, mutated recessive disease genes or of genes that cause disease when haploinsufficient) or downregulation (e.g. of mutated dominant genes which confer a gain of pathologic function or of genes which, when present in increased number, cause disease). Moreover, it is known that small molecules including clinically approved drugs can affect the human transcriptome. Given the number of genes that cause or effect inherited human conditions and the substantial subset of the transcriptome that is impacted by drugs, we believe that there are likely genes which are both modifiers of rare disease and responsive to pharmacologic modulation. The enhanced CARE for RARE project in Canada is therefore exploring whether previously unknown off-target effects of clinically approved drugs may lead to new therapies. We have screened ∼ 80 rare conditions, (haploinsufficient, rescuing paralogous genes and hypomorphic mutation with residual function) using this approach. There are currently 5 conditions which show some induction (GLUT1, SMAD3, DDHD2, NEU1, HPRT) ; the most promising results and lessons learned from this approach shall be presented.

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Objective: It was proposed to determine the chromosomal abnormalities in a 49-year-old male patient with multiple myeloma (MM) employing both conventional and advanced molecular cytogenetic techniques.Methods: GTG-banding and spectral karyotyping (SKY) on fixed metaphases obtained from LPS-stimulated bone marrow cells and interphase fluorescence in situ hybridization (iFISH) on unsorted marrow cells were carried out to identify genetic markers of prognostic significance.Results: The abnormal chromosomes observed through conventional cytogenetics could be resolved with SKY technique. The translocation t(4;14) (p16;q32) indicating FGFR3/IGH fusion and deletion of 13q14.3 was noticed using iFISH. The genetic abnormalities confirmed a poor prognostic outcome in the patient who died within 6 months of diagnosis.Conclusion: This report emphasizes the need for multicolor FISH techniques besides iFISH to resolve complex abnormalities and to identify cryptic aberrations of importance in risk stratification of MM patients.