Journal of medical genetics
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The molecular defect predisposing to the majority of malignant hyperthermia (MH) cases is unknown, although various point mutations in the ryanodine receptor gene (RYR1) have been associated with susceptibility in a small proportion of cases. We report here that one of these, the Arg163Cys substitution, does not cosegregate with MH susceptibility. Comparison of cDNA sequences encoding the skeletal muscle specific components of the dihydropyridine receptor alpha 1 subunit between MH susceptible (MHS) and MH non-susceptible (MHN) patients was made in subjects without the reported MH linked RYR1 mutations. There were no differences within the sequence encoding the II-III loop or the IS3/IS3-IS4 segment, excluding defects in these functional segments of the alpha 1 subunit as frequent causes of MH.
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We have screened two families for constitutional TP53 mutations, one family with Li-Fraumeni syndrome and the other with features of this syndrome. We report a germline mutation in exon 7 of the TP53 gene in the family with "Li-Fraumeni-like" syndrome. The mutation occurred at codon 245 and causes a Gly-Ser amino acid change. ⋯ In this family positive staining was seen in both malignant and normal tissues. These results support previous findings that variants of the Li-Fraumeni syndrome exist since not all LFS families carry TP53 germline mutations. Secondly, immunohistochemical positivity is not synonymous with an underlying mutation and is therefore inadequate as an exclusive diagnostic marker.
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We report a 20 year old man with short stature, microcephaly, unusual facies, numerous pigmented naevi, hypodontia, immunodeficiency, and a high pitched voice. Tympner et al had assumed that the patient had a new syndrome of "progressive combined immunodeficiency and ectomesodermal dysplasia". ⋯ Our patient suffered from severe viral infections, allergic rhinitis and conjunctivitis, delayed puberty, visual loss, modest achievement in high school, and reactive depression. The immunological, facioskeletal, and dental abnormalities are presented in detail.