Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptide-carrier conjugates are widely used to raise antipeptide antibodies. In a model system using angiotensin and tetanus toxoid as the peptide and the carrier protein respectively, four cross-linking reagents were employed to study their effect on the immunogenicity of the conjugates. Optimization of the conjugation method for these heterobifunctional reagents, all succinimidyl active esters, resulted in well-defined conjugates of predictable composition. ELISA assays were performed to compare the antigenicity and the immunogenicity of the conjugates. The antipeptide antibody titres were of the order of 2 X 10(4)-2 X 10(5). The anti-carrier antibody titres were high, in spite of the modification of the protein. Three of the four coupling reagents used for conjugation were of the 'maleimide' type: succinimidyl 6-(N-maleimido)-n-hexanoate (MHS), succinimidyl 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (SMCC) and succinimidyl m-maleimidobenzoate (MBS). One coupling reagent contained an activated disulphide: succinimidyl 3-(2-pyridyldithio)propionate (SPDP). The constrained linkers originating from SMCC and MBS induced very high linker-specific antibody levels. The more flexible non-aromatic linkers originating from MHS and SPDP showed almost no reactivity. For this reason and since the thioether linkage is more stable than the disulphide bond, we recommend MHS as the crosslinking reagent of choice.
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PMID:Comparison of four bifunctional reagents for coupling peptides to proteins and the effect of the three moieties on the immunogenicity of the conjugates. 249 36

Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH). Here we present two non-Native American families, who were found to have STAC3 pathogenic variants. The first proband and her affected older sister are from a consanguineous Qatari family with a suspected clinical diagnosis of Carey-Fineman-Ziter syndrome (CFZS) based on features of hypotonia, myopathic facies with generalized weakness, ptosis, normal extraocular movements, cleft palate, growth delay, and kyphoscoliosis. We identified the homozygous c.851G>C;p.Trp284Ser variant in STAC3 in both sisters. The second proband and his affected sister are from a non-consanguineous, Puerto Rican family who was evaluated for a possible diagnosis of Moebius syndrome (MBS). His features included facial and generalized weakness, minimal limitation of horizontal gaze, cleft palate, and hypotonia, and he has a history of MH. The siblings were identified to be compound heterozygous for STAC3 variants c.851G>C;p.Trp284Ser and c.763_766delCTCT;p.Leu255IlefsX58. Given the phenotypic overlap of individuals with CFZS, MBS, and NAM, we screened STAC3 in 12 individuals diagnosed with CFZS and in 50 individuals diagnosed with MBS or a congenital facial weakness disorder. We did not identify any rare coding variants in STAC3. NAM should be considered in patients presenting with facial and generalized weakness, normal or mildly abnormal extraocular movement, hypotonia, cleft palate, and scoliosis, particularly if there is a history of MH.
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PMID:Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome. 2877 91