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

Quinteiro, Celsa; Castro-Feijóo, Lidia; Loidi, Lourdes; Barreiro, J; Fuente, María de la; Domı́nguez, Fernando; Pombo, Manuel

doi:10.1515/jpem.2002.15.7.1041

Cited by 15 publications

(8 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there has been growing recognition of the use of alternate initiation codons in mammalian cells, often producing proteins with very different functions [39][40][41], as well as recognition of new mechanisms of translational control of protein structure and function [42,43]. Initiator codon mutations are uncommon, but typically they are associated with null alleles as no functional protein is produced [44][45][46][47]. However, in a few cases, translation of the mutant allele initiates from a downstream methionine or other amino acid, producing a truncated protein that retains partial or full function [48][49][50].…”

Section: Discussionmentioning

confidence: 99%

Ankyrin‐linked hereditary spherocytosis in an African–American kindred

et al. 2008

View full text Add to dashboard Cite

Mutations of ankyrin-1 are the most frequent cause of the inherited hemolytic anemia, hereditary spherocytosis (HS), in people of European ancestry. Ankyrin-1, which provides the primary linkage between the erythrocyte membrane skeleton and the plasma membrane, has numerous isoforms generated by alternative splicing, alternate polyadenylation, use of tissue-specific promoters, and alternate NH 2 or COOH-termini. Mutation detection in erythrocyte membrane protein genes, including ankyrin, has been a challenge, primarily due to the large size of these genes, and the apparent frequent occurrence of HS-associated null alleles. Using denaturing high-performance liquid chromatography (DHPLC), we screened the ankyrin gene of the proband of a large, three generation African-American kindred with ankyrin-deficient HS. DHPLC yielded an abnormal chromatogram for exon 1. Examination of the corresponding exon 1 sequence in genomic DNA from the proband revealed heterozygosity for a mutation of the initiator methionine (ATG to ATA Met 1 Ile). Coupled in vitro transcription/translation studies with rabbit reticulocyte lysates demonstrated that the wild-type ankyrin erythroid cDNA initiates only from the known initiator methionine, indicating that the use of alternate initiator methionine is not a mechanism of isoform diversity in erythroid cells. The mutant ankyrin allele, unlike some initiator methionine mutations that utilize downstream codons for translation initiation, was associated with a null allele. This is the first report describing ankyrin-linked HS in an African-American kindred. Am. J. Hematol. 83:789-794, 2008. V

show abstract

Section: Discussionmentioning

confidence: 99%

Ankyrin‐linked hereditary spherocytosis in an African–American kindred

et al. 2008

View full text Add to dashboard Cite

show abstract

“…It has been reported that alterations of the translational start codon ATG to TTG diminish or reduce the translation of growth hormone receptor (Quinteiro et al, 2002), protoporphyrinogen oxidase (Frank et al, 1999), low-density lipoprotein receptor (Langenhoven et al, 1996), and mitochondrial acetoacetylCoA thiorase (Fukao et al, 2003). Thus, it is likely that the 1AϾT variation is a low-activity variation.…”

Section: Discussionmentioning

confidence: 99%

Haplotypes and a Novel Defective Allele of CES2 Found in a Japanese Population

Kim

Sai²,

Tanaka-Kagawa³

et al. 2007

Drug Metabolism and Disposition

View full text Add to dashboard Cite

ABSTRACT:Human carboxylesterase 2 (hCE-2) is a member of the serine esterase superfamily and is responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. hCE-2 also activates an anticancer drug, irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin, CPT-11), into its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). In this study, a comprehensive haplotype analysis of the CES2 gene, which encodes hCE-2, in a Japanese population was conducted. Human carboxylesterases are members of the serine esterase superfamily and are responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. They metabolize esters, thioesters, carbamates, and amides to yield soluble acids and alcohols or amines (Satoh and Hosokawa, 1998;Satoh et al., 2002). In the human liver, two major isoforms of carboxylesterase, hCE-1 and hCE-2, have been identified (Shibata et al., 1993;Schwer et al., 1997). hCE-2 is a 60-kDa monomeric enzyme with a pI value of approximately 4.9 and shares 48% amino acid sequence identity with hCE-1 (Pindel et al., 1997;Schwer et al., 1997;Takai et al., 1997). The CES2 gene, which encodes hCE-2, is located on chromosome 16q22.1 and consists of 12 exons. Distribution of hCE-2 is relatively limited to several tissues, such as the small intestine, colon, heart, kidney, and liver, whereas hCE-1 is ubiquitously expressed (Satoh et al., 2002;Xie et al., 2002).Although both hCE-1 and hCE-2 show broad substrate specificities, hCE-2 is relatively specific for heroin, cocaine (benzoyl ester), 6-acetylmorphine, procaine, and oxybutynin (Pindel et al., 1997;Takai et al., 1997;Satoh et al., 2002). In addition, hCE-2 is reported to play a major role in the metabolic activation of the antitumor drug irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin; CPT-11). Irinotecan is a water-soluble derivative of the plant alkaloid camptothecin and is widely used for treatment of several types of cancer. Irinotecan is converted to 7-ethyl-10-hydroxy- camptothecin (SN-38), a topoisomerase inhibitor, by carboxylesterases (Humerickhouse et al., 2000) and further conjugated by hepatic uridine diphosphate glucuronosyltransferase to form the inactive metabolite SN-38 glucuronide (SN-38G) (Iyer et al., 1998). To a lesser extent, irinotecan is also converted to 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin and 7-ethyl-10-(4-amino-1-piperidino)carbonyloxycamptothecin by cytochrome P450 3A4 (Dodds et al., 1998;Santos et al., 2000). Irinotecan and its metabolites are excreted by the efflux transporters, ABCB1 (P-glycoprotein), ABCC2 (canalicular multispecific organic anion transporter), and ABCG2 (breast cancer resistance protein), via a hepatobiliary pathway (Mathijssen et al., 2001). Although irinotecan metabolism is rather complex, hCE-2 is a key enzyme that determines the plasma levels of the active metabolite SN-38. Hepatic hCE-2 activity toward irinotecan varies 3-fold in microsomes obtained from a panel of human ...

show abstract

“…18 , caused by transversion of A to T, that abolished the translation initiation codon of the GHR gene. 18 , caused by transversion of A to T, that abolished the translation initiation codon of the GHR gene.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Human Growth Hormone Receptor and IGF-I Coding Sequences in Children with Growth Disorders

Obrępalska‐Stęplowska¹,

Kędzia²,

Goździcka-Józefiak³

et al. 2003

Journal of Pediatric Endocrinology and Metabolism

View full text Add to dashboard Cite

Analysis of GHR and IGF-I coding sequences in 47 children with normal serum levels of GH, low IGF-I and growth disorders generally did not show mutation in the genes studied. Only one boy had a mutation located in the fifth exon of the GHR gene (C-->T in codon 88). This suggests that the growth disorders in this group of children might be due to a defect in a DNA region regulating expression of the GHR and IGF1 genes or genes involved in their regulation.

show abstract

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

Cited by 15 publications

References 9 publications

Ankyrin‐linked hereditary spherocytosis in an African–American kindred

Ankyrin‐linked hereditary spherocytosis in an African–American kindred

Haplotypes and a Novel Defective Allele of CES2 Found in a Japanese Population

Analysis of the Human Growth Hormone Receptor and IGF-I Coding Sequences in Children with Growth Disorders

Contact Info

Product

Resources

About