Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: A congenital disorder of glycosylation mimicking glycogen storage disease

Choi, Rihwa; Woo, Hye In; Choe, Byung-Ho; Park, Seungman; Yoon, Yoo‐Seok; Ki, Chang Seok; Lee, Soo-Youn; Kim, Jong Won; Song, Junghan; Kim, Dong Sub; Kwon, Soonhak; Park, Hyung-Doo

doi:10.1016/j.cca.2015.02.008

Cited by 12 publications

(8 citation statements)

References 18 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18 Similarly, patients clinically diagnosed with GSD have been found, by this form of analysis, to have mutations in the congenital disorder of glycosylation-associated gene PMM2. 19 Whole-exome sequencing or whole-genome sequencing of the samples from patients for whom no diagnosis was reached would be recommended.…”

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

View full text Add to dashboard Cite

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

show abstract

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

View full text Add to dashboard Cite

show abstract

“…A recent study on the genetic diagnosis of structural fetal abnormalities revealed by ultrasound reported the possibility of applying WES to fetuses [12]. In such cases, the step-wise approach of Sanger sequencing of individual genes can be time-consuming; WES could be a cost effective approach [513]. The present study highlights the potential for expanding the applicability of WES to the molecular diagnosis of UCDs.…”

mentioning

confidence: 83%

“…WES was performed as previously described [5]. Briefly, exonic sequences were enriched in the DNA sample using a SureSelect Target Enrichment kit (Agilent Technologies, Santa Clara, CA, USA).…”

mentioning

confidence: 99%

Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing

et al. 2017

Self Cite

View full text Add to dashboard Cite

Diagnosis of the urea cycle disorder (USD) carbamoyl-phosphate synthetase 1 (CPS1) deficiency (CPS1D) based on only the measurements of biochemical intermediary metabolites is not sufficient to properly exclude other UCDs with similar symptoms. We report the first Korean CPS1D patient using whole exome sequencing (WES). A four-day-old female neonate presented with respiratory failure due to severe metabolic encephalopathy with hyperammonemia (1,690 µmol/L; reference range, 11.2-48.2 µmol/L). Plasma amino acid analysis revealed markedly elevated levels of alanine (2,923 µmol/L; reference range, 131-710 µmol/L) and glutamine (5,777 µmol/L; reference range, 376-709 µmol/L), whereas that of citrulline was decreased (2 µmol/L; reference range, 10-45 µmol/L). WES revealed compound heterozygous pathogenic variants in the CPS1 gene: one novel nonsense pathogenic variant of c.580C>T (p.Gln194*) and one known pathogenic frameshift pathogenic variant of c.1547delG (p.Gly516Alafs*5), which was previously reported in Japanese patients with CPS1D. We successfully applied WES to molecularly diagnose the first Korean patient with CPS1D in a clinical setting. This result supports the clinical applicability of WES for cost-effective molecular diagnosis of UCDs.

show abstract

“…Next-generation sequencing techniques including whole-exome sequencing (WES) have now opened promising possibilities to identify the molecular background of rare metabolic disease [7] . Through the use of WES technology with one experiment, it is possible to identify pathological mutations in an ample number of selected genes that are potentially associated with the disorder being tested.…”

Section: Introductionmentioning

confidence: 99%

Pediatric patient with hyperketotic hypoglycemia diagnosed with glycogen synthase deficiency due to the novel homozygous mutation in GYS2

Szymańska

Rokicki

Wątrobińska

et al. 2015

Molecular Genetics and Metabolism Reports

View full text Add to dashboard Cite

BackgroundGlycogen synthase deficiency (glycogen storage disease 0 — GSD 0) caused by mutations in the GYS2 gene is characterized by a lack of glycogen synthesis in the liver. It is a rare condition of disturbed glycogen homeostasis in the liver with less than 30 cases reported in the literature so far.Case reportWe report a 9 year old boy diagnosed with GSD 0 due to the newly identified, highly pathogenic homozygous mutation: NM_021957.3:p.Phe574Leu/c.1720T > C in ex. 14.A random, asymptomatic hypoglycemia with ketonuria was found in this patient at the age of 7. His developmental parameters were within normal ranges. Oral glucose tolerance test showed normal baseline blood levels of glucose, insulin and lactate, and their increase following glucose intake. Eight-hour fasting plasma glucose test, revealed glucose blood level of 34 mg/dl with no clinical symptoms. The results of these tests suggested GSD 0. Molecular analysis of the GYS2 gene was not feasible, but this particular gene was included in the panel of hypoglycemia of whole exome sequencing (WES) which was at our disposal.

show abstract

Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: A congenital disorder of glycosylation mimicking glycogen storage disease

Cited by 12 publications

References 18 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

Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing

Pediatric patient with hyperketotic hypoglycemia diagnosed with glycogen synthase deficiency due to the novel homozygous mutation in GYS2

Contact Info

Product

Resources

About