Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese population

Farrugia, Rosienne; Scerri, Christian; Montalto, Simon Attard; Parascandolo, Raymond; Neville, Brian; Felice, Alex E.

doi:10.1016/j.ymgme.2006.10.013

Cited by 26 publications

(17 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, within this interval, the two Maltese sibships had a shared 1.4-Mb region of homozygosity with identical alleles at seven polymorphic markers. Such an observation was highly suggestive of an ancestral haplotype, especially as founder mutations in the Maltese population have been previously identified in two other disorders 16 . On the basis of this smaller region, we considered the AGS5 critical interval to contain 20 RefSeqannotated genes.…”

supporting

confidence: 63%

Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response

et al. 2009

View full text Add to dashboard Cite

Aicardi-Goutières syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response.

show abstract

supporting

confidence: 63%

Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response

et al. 2009

View full text Add to dashboard Cite

show abstract

“…When searching the NCBI SNP database (http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=11033026), the HapMap data, revealed that this variant was not reported in the European Caucasian population, but was found in Sub-Saharan Africans, African-Americans and Han Chinese from Beijing (minor allele frequencies 0.336, 0.115, and 0.012, respectively). This suggests a founder effect in the Maltese population, complementing other previously reported studies on other human diseases [18,19].…”

Section: Discussionsupporting

confidence: 88%

Effects of a synonymous variant in exon 9 of the CD44 gene on pre-mRNA splicing in a family with osteoporosis

Vidal

Cachia

Xuereb-Anastasi

2009

Bone

View full text Add to dashboard Cite

Edited by: M. Noda Keywords: CD44 Osteoporosis Linkage Alternative splicing RNA In a previous linkage study, suggestive linkage to osteoporosis was observed in marker D11S1392 on chromosome 11p12. The CD44 gene, found at this locus, was sequenced in one of the families studied. Sequencing all coding regions and promoter in affected and non-affected family members revealed a number of sequence variants, one of which was found to be linked and inherited identical by descent together with the linked STR allele. This G to A variant, which does not cause an amino acid change, was found in exon 9 of the CD44 gene, 32 base pairs upstream from the exon-intron junction. Preliminary analysis using a bioinformatics tool suggested that the presence of the A allele abolished an exon splicing enhancer (ESE) site, thus possibly affecting RNA splicing. It was observed using an exon-trapping vector, that in the presence of the A allele, only one transcript was observed in RAW264.7 cells, as opposed to two transcripts transcribed in the presence of the G allele. These observations suggest that the linked synonymous variant found in exon 9 of the CD44 gene might be increasing susceptibility to osteoporosis in this family by affecting the splicing mechanism.© 2009 Elsevier Inc. All rights reserved. IntroductionFor the past 15 years, numerous studies have been performed in different populations using both linkage and association approaches, to try to identify genes that might increase the individual's susceptibility to osteoporosis [1,2]. Most of these studies did not give any conclusive results, and lacked replication due to reasons such as genetic heterogeneity between different populations and low sample power. Still such studies were useful in understanding better the complex pathophysiology of osteoporosis by identifying genes playing a role in various metabolic pathways and other mechanisms that might lead to disease. Linkage studies of monogenic bone diseases revealed several chromosomal regions putting into light various genes that were never thought to be involved in bone physiology such as the low density lipoprotein receptor-related protein (LRP)-5 and sclerostin (SOST) genes [3,4].In a previous linkage study, performed on two Maltese families with a high incidence of osteoporosis, suggestive linkage to chromosome 11p12 was observed [5]. Fine-mapping reduced the linkage interval to a region between markers D11S1392 (50.64 cM) and D11S935 (52.94 cM), with highest total heterogeneity LOD and NPL (3.07 and 7.0, respectively) to marker D11S935. Although both families shared the same linkage interval, highest LOD scores were obtained to two different markers with a spacing of approximately 4 cM between them, showing also different inherited alleles, thus suggesting that different genes might be responsible for the disease in different families [5]. Highest LOD and NPL scores (1.77 and 5.9, respectively) were obtained for marker D11S1392 (50.64 cM) in Pedigree 2, while for Pedigree 1 highest scores were obtained to marker D11S4...

show abstract

“…R150G), deletion mutations (e.g. Q119X), as well as splicing mutations (IVS2-2AϾG) (57,58). That sepiapterin reductase is crucial for neuronal functioning has been highlighted recently by findings that sepiapterin reductase knock-out mice have reduced levels of neurotransmitters and that this is associated with a variety of movement disorders (59,60).…”

Section: Discussionmentioning

confidence: 99%

Sepiapterin Reductase Mediates Chemical Redox Cycling in Lung Epithelial Cells

Yang¹,

Jan

Gray

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Enzymes mediating chemical redox cycling in the lung are poorly defined. Results: Sepiapterin reductase was identified as a key mediator of redox cycling and was analyzed using inhibitors and sitedirected mutagenesis. Conclusion: Sepiapterin reductase generates reactive oxygen species during redox cycling in a mechanism distinct from sepiapterin reduction. Significance: This is the first report demonstrating that sepiapterin reductase mediates chemical redox cycling.

show abstract

Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese population

Cited by 26 publications

References 19 publications

Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response

Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response

Effects of a synonymous variant in exon 9 of the CD44 gene on pre-mRNA splicing in a family with osteoporosis

Sepiapterin Reductase Mediates Chemical Redox Cycling in Lung Epithelial Cells

Contact Info

Product

Resources

About