Ornithine transcarbamylase deficiency: Ten new mutations and high proportion of de novo mutations in heterozygous females

Leibundgut, Elisabeth Oppliger; Liechti‐Gallati, Sabina; Colombo, Jean‐Pierre; Wermuth, Bendicht

doi:10.1002/(sici)1098-1004(1997)9:5<409::aid-humu5>3.0.co;2-z

Cited by 12 publications

(1 citation statement)

References 10 publications

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“…In our laboratory we have developed a two buffer PAGE (polyacrylamide gel electrophoresis) system-based protocol combining SSCP and HD analysis and allowing the detection of at least 97% of all mutations within the entire coding sequence of the CFTR gene (including intron/exon boundaries) independent of their nature, frequency, and geographic or ethnic origin. 30,31 This protocol represents a general model for rapid and reliable mutation analysis in any genetic disorder and has already been successfully established for 20 different nuclear gene loci 32,33 as well as for the entire mitochondrial genome. 34,35 For patients with pathological or borderline sweat test and/or typical CF symptoms, where no or only one CF mutation is identifiable on the gene (DNA) level, we offer quantitative and qualitative transcript (RNA) analysis allowing the detection of large deletions, alternatively spliced transcription products, as well as reduced transcriptional efficiency.…”

Section: Genetic Testing For Cystic Fibrosismentioning

confidence: 99%

Genetics of Cystic Fibrosis

Gallati

2003

Seminars in Respiratory and Critical Care Medicine

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Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes a protein expressed in the apical membrane of exocrine epithelial cells. CFTR functions principally as a cyclic adenosine monophosphate (cAMP)-induced chloride channel and appears capable of regulating other ion channels. Mutations affect CFTR through a variety of molecular mechanisms, which can produce little or no functional gene product at the apical membrane. More than 1000 different disease-causing mutations within the CFTR gene have been described. The potential of a mutation to contribute to the phenotype depends on its type, localization in the gene, and the molecular mechanism as well as on interactions with secondary modifying factors. Genetic testing can confirm a clinical diagnosis of CF and can be used for infants with meconium ileus, for carrier detection in individuals with positive family history and partners of proven CF carriers, and for prenatal diagnostic testing if both parents are carriers. Studies of clinical phenotype in correlation with CFTR genotype have revealed a very complex relationship demonstrating that some phenotypic features are closely determined by the underlying mutations, whereas others are modulated by modifier genes, epigenetic mechanisms, and environment.

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Section: Genetic Testing For Cystic Fibrosismentioning

confidence: 99%

Genetics of Cystic Fibrosis

Gallati

2003

Seminars in Respiratory and Critical Care Medicine

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De Novo Mutations in Human Inherited Disease

Oliveira

Cooper

Azevedo

2018

Encyclopedia of Life Sciences

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Mutations and polymorphisms in the human ornithine transcarbamylase gene

et al. 2002

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Ornithine transcarbamylase (OTC) deficiency, an X-linked, semidominant disorder, is the most common inherited defect in ureagenesis resulting in hyperammonemia. The previous two mutation updates for the OTC gene were published in 1993 and 1995 and included 36 and 30 mutations respectively. This comprehensive update contains a compilation of 244 mutations including 13 polymorphisms. Twenty-four of the mutations are reported here for the first time. Forty-two percent of the disease-causing mutations are associated with acute neonatal hyperammonemia; 21% were found in patients with late onset disease and approximately 37% were found in manifesting heterozygous females, most of which are presumed to confer a neonatal phenotype in hemizygous males. Also included are residual enzyme activities and residual incorporation of ammonium nitrogen into urea and results of expression studies for a small proportion of the mutations. Most mutations in the OTC gene are "private" and are distributed throughout the gene with paucity of mutation in the sequence encoding the leader peptide (exon 1 and beginning of exon 2) and in exon 7. Almost all mutations in consensus splicing sites confer a neonatal phenotype. Thirteen polymorphisms have been found, several of which are useful for allele tracking in patients in whom the mutation can't be found. Even with sequencing of the entire reading frame and exon/intron boundaries, only about 80% of the mutations are detected in patients with proven OTC deficiency. The remaining probably occur within the introns or in regulatory domains.

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Ornithine transcarbamylase deficiency: Ten new mutations and high proportion of de novo mutations in heterozygous females

Cited by 12 publications

References 10 publications

Genetics of Cystic Fibrosis

Genetics of Cystic Fibrosis

De Novo Mutations in Human Inherited Disease

Mutations and polymorphisms in the human ornithine transcarbamylase gene

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