A novel β-thalassemia mutation (G→A) at the initiation codon of the β-globin gene

Saba, Luisella; Meloni, Alessandra; Sardu, R; Travi, Maurizio; Primignani, Paola; Rosatelli, Maria Cristina; Cao, Antonio

doi:10.1002/humu.1380010512

Cited by 16 publications

(7 citation statements)

References 11 publications

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“…In other genes, mutations of this kind have been found to severely disturb correct translation initiation and usually are associated with a phenotypic expression similar to that of null mutations (HBB, CFTR). 30,31 We also identified no mutation in the recently described exons, 19 6A and 16A, in these patients. We identified no TCOF1 gene mutation in any of the 10 patients with tentative diagnosis of TCS.…”

Section: Tcof1 Gene Mutations In Patients With Tcssupporting

confidence: 51%

Genotyping in 46 patients with tentative diagnosis of Treacher Collins syndrome revealed unexpected phenotypic variation

et al. 2004

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To define the range of phenotypic expression in Treacher Collins syndrome (TCS; Franceschetti-Klein syndrome), we performed mutation analysis in the TCOF1 gene in 46 patients with tentative diagnosis of TCS and evaluated the clinical data, including a scoring system. A total of 27 coding exons of TCOF1 and adjacent splice junctions were analysed by direct sequencing. In 36 patients with a clinically unequivocal diagnosis of TCS, we detected 28 pathogenic mutations, including 25 novel alterations. No mutation was identified in the remaining eight patients with unequivocal diagnosis of TCS and 10 further patients, in whom the referring diagnosis of TCS was clinically doubtful. There is no overt genotype-phenotype correlation except that conductive deafness is significantly less frequent in patients with mutations in the 3 0 part of the open reading frame. Inter-and intrafamilial variation is wide. Some mutation carriers, parents of typically affected patients, are so mildly affected that the diagnosis might be overlooked clinically. This suggests that modifying factors are important for phenotypic expression. Based on these findings, minimal diagnostic criteria were defined: downward slanting palpebral fissures and hypoplasia of the zygomatic arch. The difficulties in genetic counselling, especially diagnosis of family members with a mild phenotype, are described.

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Section: Tcof1 Gene Mutations In Patients With Tcssupporting

confidence: 51%

Genotyping in 46 patients with tentative diagnosis of Treacher Collins syndrome revealed unexpected phenotypic variation

et al. 2004

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“…Point mutations in the translation initiation codon have been described in several other inherited diseases: for example, mutations to ACG, to GTG, and to ATA in the P-globin gene causing P-thalassemia (Jankovic et al, 1990;Hattori et al, 1991;Saba et al, 1992), a mutation to ATA in the phenylalanine hydroxylase gene causing phenylketonuria (Eiken et al, 1992), and mutations to G T G and to ACG in the P-hexosaminidase a-subunit gene causing Tay-Sachs disease (Mules et al, 1992;Harmon et al, 1993). The unusual association of McArdle's disease and scleroderma raises the question of a possible common pathogenetic mechanism.…”

Section: Resultsmentioning

confidence: 99%

An A-to-C substitution involving the translation initiation codon in a patient with myophosphorylase deficiency (McArdle's disease)

et al. 1994

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“…The 18 residues contain a hydrophobic core flanked by charged amino acids that indicate a membrane signal. This type of mutation has been found in some other hereditary diseases, with catastrophic results, such as ß-thalassemia (ßglobin gene) 18 , phenylketonuria (phenylalanine hydroxylase gene) 19 , Tay-Sachs disease (ß-hexosaminidase α-subunit gene) 20 Signal transduction of GH is initiated by binding a single GH molecule to its receptor, followed by GHR dimerization 23 . We believe that the mutation we have identified completely prevents the translation of the receptor because the ATG codon is essential for the initiation of translation of genes in higher eukaryotes 15 ' 16 .…”

Section: Discussionmentioning

confidence: 99%

Novel Mutation Involving the Translation Initiation Codon of the Growth Hormone Receptor Gene (GHR) in a Patient with Laron Syndrome

Quinteiro

Castro-Feijóo²,

Loidi³

et al. 2002

Journal of Pediatric Endocrinology and Metabolism

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Laron syndrome (LS) or growth hormone (GH) insensitivity syndrome (GHIS) is an autosomal recessive disease due to molecular defects in the GH receptor gene (GHR). Most of the identified mutations are located on the extracelular domain of the receptor. We studied the GHR gene in a patient with LS and found a homozygous missense mutation in exon 2. The novel mutation is an A->T transversion (ATG ->TTG) that abolishes the translation initiation codon of the GHR gene. This mutation is expected to prevent the translation of the protein.We present clinical, biochemical and molecular evidence of Laron syndrome as the result of a mutation (ATG->TTG) in the codon for the initial methionine of the GHR gene.

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A novel β-thalassemia mutation (G→A) at the initiation codon of the β-globin gene

Cited by 16 publications

References 11 publications

Genotyping in 46 patients with tentative diagnosis of Treacher Collins syndrome revealed unexpected phenotypic variation

Genotyping in 46 patients with tentative diagnosis of Treacher Collins syndrome revealed unexpected phenotypic variation

An A-to-C substitution involving the translation initiation codon in a patient with myophosphorylase deficiency (McArdle's disease)

Novel Mutation Involving the Translation Initiation Codon of the Growth Hormone Receptor Gene (GHR) in a Patient with Laron Syndrome

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