Molecular analysis of the AGL gene: Identification of 25 novel mutations and evidence of genetic heterogeneity in patients with Glycogen Storage Disease Type III

Goldstein, Jennifer; Austin, Stephanie; Boyette, Keri; Kanaly, Angela; Veerapandiyan, Aravind; Rehder, Catherine; Kishnani, Priya S.; Bali, Deeksha

doi:10.1097/gim.0b013e3181d94eaa

Cited by 44 publications

(52 citation statements)

References 45 publications

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“…This type of mutation accounts for nearly 82% of those deposited for this gene in the Human Gene Mutation Database. [13][14][15] Missense mutations are scarce. 13,16,17 No mutation was prevalent, but c.348_373del26 was present in three mutant alleles (21%).…”

Section: Discussionmentioning

confidence: 99%

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Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing

Vega

Medrano

Navarrete

et al. 2016

Genetics in Medicine

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Purpose: Glycogen storage disease (GSD) is an umbrella term for a group of genetic disorders that involve the abnormal metabolism of glycogen; to date, 23 types of GSD have been identified. The nonspecific clinical presentation of GSD and the lack of specific biomarkers mean that Sanger sequencing is now widely relied on for making a diagnosis. However, this gene-by-gene sequencing technique is both laborious and costly, which is a consequence of the number of genes to be sequenced and the large size of some genes. Methods:This work reports the use of massive parallel sequencing to diagnose patients at our laboratory in Spain using either a customized gene panel (targeted exome sequencing) or the Illumina Clinical-Exome TruSight One Gene Panel (clinical exome sequencing (CES)). Sequence variants were matched against biochemical and clinical hallmarks.Results: Pathogenic mutations were detected in 23 patients. Twenty-two mutations were recognized (mostly loss-of-function mutations), including 11 that were novel in GSD-associated genes. In addition, CES detected five patients with mutations in ALDOB, LIPA, NKX2-5, CPT2, or ANO5. Although these genes are not involved in GSD, they are associated with overlapping phenotypic characteristics such as hepatic, muscular, and cardiac dysfunction. Conclusions:These results show that next-generation sequencing, in combination with the detection of biochemical and clinical hallmarks, provides an accurate, high-throughput means of making genetic diagnoses of GSD and related diseases. Genet Med advance online publication 25 February 2016

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Section: Discussionmentioning

confidence: 99%

“…[13][14][15] Missense mutations are scarce. 13,16,17 No mutation was prevalent, but c.348_373del26 was present in three mutant alleles (21%). Loss-of-function mutations in PHKA2 made up nearly 71% of the total; only 50% of the mutations deposited for this gene in the Human Gene Mutation Database belong to this category.…”

Section: Discussionmentioning

confidence: 99%

Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing

Vega

Medrano

Navarrete

et al. 2016

Genetics in Medicine

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“…Molecular analyses of GSD III patients have been performed in several ethnic populations, and over 100 different AGL mutations have been described (Goldstein et al 2010), but new mutations are still being reported (http://www.hgmd.org). No clear genotype-phenotype relationship has been established so far, although there is a relation between mutations in exon 3 and the IIIb subtype (Shen et al 1996;Shen and Chen 2002).…”

Section: Introductionmentioning

confidence: 99%

“…It is unclear, however, what mechanism enables patients with mutations in exon 3 to retain GDE activity in muscle tissue. A possible explanation was proposed by Goldstein et al (2010) in which the exon 3 mutation is bypassed using a downstream start codon, thus creating an isoform without the exon 3 mutations.…”

Section: Introductionmentioning

confidence: 99%

Mutation Analysis in Glycogen Storage Disease Type III Patients in the Netherlands: Novel Genotype-Phenotype Relationships and Five Novel Mutations in the AGL Gene

et al. 2012

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“…In addition, some mutations have been found to show geographical variation (14). Recently, a literature review reported 112 different mutations in AGL gene (15).…”

Section: Introductionmentioning

confidence: 99%

Glikojen depo hastalığı tip III tanılı 10 Türk olgunun mutasyon analizleri: dört yeni mutasyonun tanımlanması

Manguoğlu¹,

Uygun²,

Özkaya³

et al. 2012

Tpa

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Aim: AGL gene mutations are responsible for glycogen storage disease type III which is an autosomal recessive disorder. The distribution of these mutations shows a great variance in different populations. The aim of this study is to uncover the AGL gene mutation profile among Turkish patients and to contribute to the establishment of a link between these mutations and the clinical picture of the disease. Material and Method: A total of ten patients aged between two and eight years (mean age 1.7+1.1) who were diagnosed with glycogen storage disease type III by liver biopsy and enzymatic analysis from eight different families were included in this study. DNA was isolated from the peripheral blood samples of these patients and exons 6, 7, 9-18, 22, 24, 29-34 of the AGL gene were studied by DNA sequencing analysis. Results: Our study revealed two novel missense mutations p.G167V and p.Y173F , two novel intronic single base substitutions c.1284-1G>A and c.2002-2A>T and a known single base substitution p.W1327X. Numerous intronic variants were also identified. As a result of the analysis of ten patients, SNP's rs3736296, IVS12-197T>G, rs2291637, rs2035961, rs2274570, rs6692695, rs296885 were found in 1, 6, 1, 1, 1, 1, and 2 of the 10 patients, respectively. Conclusions: According to the recent literature about the AGL gene which is constituted of a total of 35 coding exons, mutations have been reported frequently in exons 3, 4, 7, 16, 21, 25, 30 and 31. This study and previous studies reveal that the majority of the mutations identified in Turkish patients so far have been detected in exon 31 of the AGL gene. In addition, the distribution of AGL gene mutations in Turkish patients reflects the genetic heterogeneity in our population. (Turk Arch Ped 2012; 47: 274-278)

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Molecular analysis of the AGL gene: Identification of 25 novel mutations and evidence of genetic heterogeneity in patients with Glycogen Storage Disease Type III

Cited by 44 publications

References 45 publications

Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing

Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing

Mutation Analysis in Glycogen Storage Disease Type III Patients in the Netherlands: Novel Genotype-Phenotype Relationships and Five Novel Mutations in the AGL Gene

Glikojen depo hastalığı tip III tanılı 10 Türk olgunun mutasyon analizleri: dört yeni mutasyonun tanımlanması

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