Disease relevance of SHFM1

• Split hand-split foot malformation (SHFM) is a genetically heterogeneous limb developmental defect characterised by the absence of digital rays and syndactyly of the remaining digits [1].
• Split hand/split foot malformation with hearing loss: first report of families linked to the SHFM1 locus in 7q21 [2].
• Bilateral complete radioulnar synostosis associated with ectrodactyly and sensorineural hearing loss: a variant of SHFM1 [3].
• Deletion or mutation of DSS1 or suppression of its expression by other mechanisms are therefore potential causative mechanisms for human breast and ovarian cancer [4].
• Most notably, like BRCA2 depletion, DSS1 depletion also led to hypersensitivity to DNA damage [4].

Psychiatry related information on SHFM1

• The present study investigated if acute treatment with tetrahydroaminoacridine (THA) (25 or 75 mg, p.o.) affects technetium-99m labelled ethylene dicysteinate (ECD) retention abnormalities in patients with mild to moderate Alzheimer's disease (AD; mean age 69 years) [5].
• CONCLUSION: The authors cannot demonstrate the pattern of hypoperfusion of 99-Tc ECD SPECT among patients' difference in dementia severity [6].

High impact information on SHFM1

• The influence of the concentration of androgen present on the development of heterogeneous growth responsiveness to androgens was studied in an androgen-sensitive clone (SEM-1) of the Shionogi mammary carcinoma cell line incubated for up to 6 months in the presence of 0, 0.01, 0.3, or 100 nM dihydrotestosterone (DHT) [7].
• Bronchodilatation was greater at 1600 h than at 0400 h in both the normal subjects (mean decrease in Ros 1-3 min after capsaicin at 1600 h 9% [SEM 1], at 0400 h -2% [1]; p less than 0.001) and the asthmatic group (1% [1], -7% [2]; p = 0.001) [8].
• There appears to be a genotype-phenotype correlation, in that there is a specific pattern of missense mutations in EEC syndrome that are not generally found in SHFM or LMS [9].
• Split-hand/split-foot malformation (SHFM), a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals, is phenotypically analogous to the naturally occurring murine Dactylaplasia mutant (Dac) [10].
• We mapped data from a large Turkish family with isolated SHFM to chromosome 10q24 and have narrowed the SHFM3 region from 9 cM to an approximately 2-cM critical interval between genetic markers D10S1147 and D10S1240 [11].

Chemical compound and disease context of SHFM1

• It was found that the required hypotension (51 (SEM 1) mmHg) could be obtained and maintained at much lower isoflurane concentrations (less than 1%) after blockade of the angiotensin converting enzyme activity by enalaprilat (2.5 mg i.v.) than without such inhibition [12].
• The methods available for routing CBF tomography in acute stroke cases are discussed, and it is concluded that single photon emission computed tomography (SPECT) using [99mTc]hexamethyl propyleneamine oxide (HM-PAO) or [99mTc]ethyl cysteinate dimer (ECD) should be explored for this use [13].
• Statistical parametric mapping and statistical probabilistic anatomical mapping analyses of basal/acetazolamide Tc-99m ECD brain SPECT for efficacy assessment of endovascular stent placement for middle cerebral artery stenosis [14].

Biological context of SHFM1

• Three disease loci have recently been mapped to chromosomes 7q21 (SHFM1), Xq26 (SHFM2), and 10q25 respectively (SHFM3) [1].
• To investigate 10q25 as a possible split hand/split foot locus, microsatellite markers spanning 52 cM of 10q were utilized for linkage analysis of a large autosomal dominant SHSF pedigree in which the region encompassing SHFM1 previously was excluded as containing the causative mutation [15].
• However, incomplete penetrance, variable expressivity, segregation distortion, and syndromic association with other anomalies have so far prevented the identification of the SHFM1 gene(s) in man [16].
• Molecular genetic characterization of a Korean split hand/split foot malformation (SHFM) [17].
• In the present study, marker loci were localized to the SHFD1 critical region through the analysis of somatic cell hybrids derived from individuals with SHSF and cytogenetic abnormalities involving the 7q21-q22 region [18].

Anatomical context of SHFM1

• Here we show that the targeted double inactivation of Dlx5 and Dlx6 in the mouse causes in homozygous mutant animals bilateral ectrodactyly with a severe defect of the central ray of the hindlimbs, a malformation typical of SHFM1 [16].
• SHFM is clinically heterogeneous, presenting both in an isolated form and in combination with additional abnormalities affecting the tibia and/or other organ systems, including the genitourinary, craniofacial, and ectodermal structures [11].
• Importantly, we found that RNAi knockdown of DSS1 in human cell lines led to dramatic loss of BRCA2 protein, mainly due to its increased degradation [4].
• Although 64 (SEM 4)% of the local inflammatory cells expressed Ia antigen, only 4 (SEM 1)% of them displayed the T cell activation antigen Tac [19].
• Discrepancies in upper and lower limb patterning in split hand foot malformation.Split hand foot malformation (SHFM) is genetically heterogeneous with five loci mapped to date [20].

Associations of SHFM1 with chemical compounds

• Here we report that although Calindol has little or no agonist activity in the absence of extracellular Ca(2+) for the ECD-containing wild type or carboxyl-terminal deleted receptors, it acts as a strong agonist of the T903-Rhoc [21].
• Valine metabolism was investigated in five normal and three nondialyzed chronically uremic subjects eating 40 +/- SEM 1 and 53 (range 40 to 80) protein diets respectively, in a metabolic research unit [22].
• The integrin-binding motifs RGD and ECD, present in the pro- and in mature forms of cathepsin X, respectively, suggest that this enzyme might have a function in cell signaling and adhesion [23].
• In this paper, we use N-pentafluorobenzoylmethionylglycine-N-hydroxysuccinimide ester, our first GC-ECD release tag, to determine thyroxin in serum by a method called "labeling analysis," which involves the principle of isotope-derivative analysis [24].
• A variety of 99mTc-labelled agents is now available or in clinical evaluation for the study of brain perfusion (99mTc-labelled HMPAO, ECD, MRP20), myocardial perfusion (99mTc-labelled MIBI, teboroxime and phosphines) and renal function (99mTc-MAG3, 99mTc-L,L-EC) [25].

Physical interactions of SHFM1

• DSS1 is an evolutionarily conserved acidic protein that binds to BRCA2 [4].

Other interactions of SHFM1

• Clinical features were variable, but limited to the four limbs unlike SHFM1, SHFM4 and SHFM5 [17].
• It therefore appears that the Korean SHFM may be caused by mutation of SHFM3 [17].
• We report the mapping of SHFM3 to chromosome 10q25 in two large SHFM families of French ancestry (Zmax for the combined families = 6.62 at theta = 0 for marker AFM249wc5 at locus D10S222) [1].
• We found that essentially all BRCA2 in human cell lines is associated with DSS1 [4].
• BRCA2-RAD51-DSS1 interplay examined from a microbial perspective [26].

Analytical, diagnostic and therapeutic context of SHFM1

• However, study of the function of DSS1 in mammalian cells has been hampered because endogenous DSS1 has not been detectable by Western blotting [4].
• In our ongoing studies of the SHFM3 locus in 44 additional cases of syndromic and non-syndromic SHFM, we have identified similar chromosome rearrangements in eight additional cases (18%), using pulsed-field gel electrophoresis (PFGE) [27].
• Somatic cell hybrid and fluorescent in situ hybridization analyses were used to define SHSF-associated chromosomal rearrangements in twelve patients [28].
• METHODS: A total of 247 patients with dyspeptic symptoms (166 women, mean age 44 (SEM 1) year), with a negative upper gastrointestinal endoscopy and without dominant symptoms of heartburn participated in the study [29].
• These electrophores are measured with high sensitivity and specificity by gas chromatography with electron-capture detection (GC-ECD) [24].

References