Whole Exome Sequencing Identified a Novel Heterozygous Mutation in HMBS Gene in a Chinese Patient With Acute Intermittent Porphyria With Rare Type of Mild Anemia

Zheng, Yu; Xu, Jibin; Liang, Shengran; Lin, Dongjun; Banerjee, Santasree

doi:10.3389/fgene.2018.00129

Cited by 44 publications

(38 citation statements)

References 10 publications

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“…In recent years, this rare disorder has garnered attention from Chinese physicians, and small series of and case reports on AIP, and especially reports of novel mutations, have increased in China, indicating that AIP may not be as "rare" as was previously assumed (108)(109)(110)(111)(112)(113)(114). In addition, some studies have analyzed clinical features of Chinese patients with AIP, such as posterior reversible encephalopathy syndrome (110,(115)(116)(117)(118).…”

Section: Status Of Research On Aip In Chinamentioning

confidence: 99%

Recent advances in the epidemiology and genetics of acute intermittent porphyria

Tian

Peng

et al. 2020

IRDR

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Acute intermittent porphyria (AIP) is a dominant inherited disorder with a low penetrance that is caused by mutations in the gene coding for hydroxymethylbilane synthase (HMBS). Information about the epidemiology and molecular genetic features of this rare disorder is crucial to clinical research, and particularly to the evaluation of new treatments. Variations in the prevalence and penetrance of AIP in various studies may due to the different inclusion criteria and methods of assessment. Here, the prevalence and penetrance of AIP are analyzed systematically, and the genetic traits of different populations and findings regarding the genotype-phenotype correlation are summarized. In addition, quite a few studies have indicated that AIP susceptibility was affected by other factors, such as modifying genes. Findings regarding possible modifying genes are documented here, helping to reveal the pathogenesis of and treatments for AIP. The status of research on AIP in China reveals the lack of epidemiological and genetic studies of the Chinese population, a situation that needs to be promptly remedied.

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Section: Status Of Research On Aip In Chinamentioning

confidence: 99%

Recent advances in the epidemiology and genetics of acute intermittent porphyria

Tian

Peng

et al. 2020

IRDR

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“…WES is the most sophisticated and advanced technique considering for identifying the candidate gene variants. allowing clinicians for making timely and proper clinical diagnosis [33][34][35]. In conclusion, our present study not only report the rst variant of SUOX gene in a patient with ISOD in Chinese population, but also describe the importance and application of WES as a potential high throughput sequencing technology for molecular genetic analysis for the patients with ISOD.…”

Section: Discussionmentioning

confidence: 66%

Whole Exome Sequencing Identified Novel Mutation in SUOX Gene Causes Extremely Rare Autosomal Recessive Isolated Sulfite Oxidase Deficiency

Zhang

Qin

et al. 2020

Preprint

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Background: Isolated sulfite oxidase deficiency (ISOD) is the rarest types of life-threatening neurometabolic disorders characterized by neonatal intractable seizures and severe developmental delay with an autosomal recessive mode of inheritance. ISOD is extremely rare and only 29 mutations have been identified and reported worldwide. Germline mutation in SUOX gene causes ISOD. Results: Here, we investigated a 5-days old Chinese girl, presented with intermittent tremor or seizures of limbs, neonatal encephalopathy, subarachnoid cyst and haemorrhage, dysplasia of corpus callosum, neonatal convulsion, respiratory failure, cardiac failure, hyperlactatemia, severe metabolic acidosis, hyperglycemia, hyperkalemia, moderate anemia, atrioventricular block and complete right bundle branch block. Karyotype and chromosomal microarray analysis were performed and identified no chromosomal abnormalities in the proband. Whole exome sequencing was performed for the proband. Sanger sequencing was performed for the proband and her family members. Whole exome sequencing identified a novel heterozygous deletion (c.1406_1421delCCTGGCAGGTGGCTAA) and a previously reported heterozygous substitution (c.1200C>G) in exon 6 of the SUOX gene in the proband. The novel heterozygous deletion leads to frameshift (p.Thr469Serfs*20) which results into the formation of a truncated sulfite oxidase of 488 amino acids. The substitution leads to a premature stop codon (p.Tyr400*) followed by the formation of a truncated sulfite oxidase of 399 amino acids. Hence, both the variants are loss-of-function variants. The proband’s father and mother is carrying the substitution and deletion in a heterozygous state respectively. These two variants were not identified in the elder brother of the proband as well as in the 100 healthy individuals. Conclusion: Here, we reported the first variant of SUOX gene associated ISOD in Chinese population. Our study not only expand the mutational spectrum of SUOX gene associated ISOD, but also strongly suggested the application of whole exome sequencing for identifying the novel disease-causing mutation in candidate genes.

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“…This is the first instance in Argentina where these variants were found together in the same individual, being one of them a de novo mutation. It is interesting to note that de novo mutations are very rare events in porphyrias [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Acute Intermittent Porphyria in a Man with Dual Enzyme Deficiencies

Cerbino

Assali

Varela

et al. 2020

Case Reports in Genetics

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Porphyrias are a heterogeneous group of metabolic disorders that result from the altered activity of specific enzymes of the heme biosynthetic pathway and are characterized by accumulation of pathway intermediates. Porphyria cutanea tarda (PCT) is the most common porphyria and is due to deficient activity of uroporphyrinogen decarboxylase (UROD). Acute intermittent porphyria (AIP) is the most common of the acute hepatic porphyrias, caused by decreased activity of hydroxymethylbilane synthase (HMBS). An Argentinean man with a family history of PCT who carried the UROD variant c.10_11insA suffered severe abdominal pain. Biochemical testing was consistent with AIP, and molecular analysis of HMBS revealed a de novo variant: c.344 + 2_ + 5delTAAG. This is one of the few cases of porphyria identified with both UROD and HMBS mutations and the first confirmed case of porphyria with dual enzyme deficiencies in Argentina.

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Whole Exome Sequencing Identified a Novel Heterozygous Mutation in HMBS Gene in a Chinese Patient With Acute Intermittent Porphyria With Rare Type of Mild Anemia

Cited by 44 publications

References 10 publications

Recent advances in the epidemiology and genetics of acute intermittent porphyria

Recent advances in the epidemiology and genetics of acute intermittent porphyria

Whole Exome Sequencing Identified Novel Mutation in SUOX Gene Causes Extremely Rare Autosomal Recessive Isolated Sulfite Oxidase Deficiency

Acute Intermittent Porphyria in a Man with Dual Enzyme Deficiencies

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