European journal of human genetics : EJHG
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Eur. J. Hum. Genet. · Jan 2001
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a Dutch family: evidence for a TNFRSF1A mutation with reduced penetrance.
Mutations of the tumor necrosis factor receptor 1 (TNFRSF1A) gene underly susceptibility to a subset of autosomal dominant recurrent fevers (ADRFs). We report on a two-generation six-member Dutch family in which a novel R92P mutation and reduced plasma TNFRSF1A levels were found in all the children, including two who are unaffected. ⋯ PCR-RFLP analysis revealed that the mutation was not present in 120 control chromosomes from unaffected Dutch individuals. As this R92P mutation is present in two unaffected carriers it appears to be less penetrant than previously reported TNFRSF1A mutations involving cysteine residues in the extracellular domains.
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Eur. J. Hum. Genet. · Feb 2000
Case ReportsIdentification of a novel mutation in the ryanodine receptor gene (RYR1) in a malignant hyperthermia Italian family.
Malignant hyperthermia (MH) is an inherited autosomal dominant pharmacogenetic disorder and is one of the main causes of death subsequent to anaesthesia. Around 50% of affected families are linked to the ryanodine receptor (RYR1) gene. To date, 19 mutations have been identified in the coding region of this gene and appear to be associated with the MH-susceptible phenotype. Here we report the identification by two independent methods of a novel mutation associated with the MH-susceptible phenotype in the RYR1 gene: the 6488G-->C transversion, resulting in the replacement of the Arg2163 with a proline residue.
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Eur. J. Hum. Genet. · Sep 1999
Clinical and morphological correlations for transglutaminase 1 gene mutations in autosomal recessive congenital ichthyosis.
Autosomal recessive congenital ichthyosis (ARCI) is a group of inherited disorders of cornification in which progress has recently been made in the identification of pathogenic mechanisms causing the disease. Transglutaminase 1 (TGM1) has been found as a defective gene in a large fraction of patients with lamellar ichthyosis (LI), a severe inherited scaling disorder of the skin. We have previously performed molecular genetic studies of 38Finnish ARCI families and found six different mutations in 13 families of 38 (34%). ⋯ Although electron microscopy is not always used to classify ARCI patients, it can distinguish groups which are parallel with molecular genetic findings. This finding might be useful in the classification of ARCI patients for further linkage studies. Clinically typical phenotype of the TGM1 mutation carrier includes large, thick, brownish scales, but ichthyosis of some of these patients tends to be milder.
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Eur. J. Hum. Genet. · May 1999
A case of discordance between genotype and phenotype in a malignant hyperthermia family.
Malignant hyperthermia (MH) is an inherited autosomal dominant pharmacogenetic disorder and is the major cause of anaesthesia-induced death. Malignant hyperthermia susceptibility is usually diagnosed by the in vitro contracture test (IVCT) performed on fresh muscle biopsies exposed to caffeine and halothane, respectively. Around 50% of affected families are linked to the ryanodine receptor (RYR1) gene. ⋯ To date, 17 mutations have been identified in the coding region of the RYR1 gene and appear to be associated to the MH-susceptible phenotype. Here we describe a rare case of discordance between genotype (characterised by the presence of the Arg614Cys mutation in the RYR1 gene) and MH-normal typed phenotype. Although the IVCT remains a very reliable procedure for the assessment of MH status, genetic data can provide in some cases an additional aid to clinical diagnosis.
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Eur. J. Hum. Genet. · Jan 1996
Case ReportsAutosomal recessive lamellar ichthyosis and acute lymphoblastic leukemia.
Autosomal recessive lamellar ichthyosis (ARLI) is a congenital disorder of keratinization, the gene of which has been mapped to chromosome 14q11. This band is also the breakpoint in various chromosomal rearrangements in T cell acute lymphoblastic leukemia (ALL). ⋯ High resolution banding showed no abnormality or rearrangement involving chromosome 14. To our knowledge, this is the first description of the occurrence of the two conditions in one patient.