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
Acute intermittent porphyria (AIP) is a rare hereditary metabolic disease with an autosomal dominant mode of inheritance. Germline mutations of HMBS gene causes AIP. Mutation of HMBS gene results into the partial deficiency of the heme biosynthetic enzyme hydroxymethylbilane synthase. AIP is clinica...
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fgene.2018.00129/full |
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doaj-2605f8f226124d16b3db173e087526b92020-11-25T00:16:53ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-04-01910.3389/fgene.2018.00129344976Whole Exome Sequencing Identified a Novel Heterozygous Mutation in HMBS Gene in a Chinese Patient With Acute Intermittent Porphyria With Rare Type of Mild AnemiaYongjiang Zheng0Jiehua Xu1Shengran Liang2Dongjun Lin3Santasree Banerjee4Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaSchool of Life Sciences and Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Hangzhou, ChinaAcute intermittent porphyria (AIP) is a rare hereditary metabolic disease with an autosomal dominant mode of inheritance. Germline mutations of HMBS gene causes AIP. Mutation of HMBS gene results into the partial deficiency of the heme biosynthetic enzyme hydroxymethylbilane synthase. AIP is clinically manifested with abdominal pain, vomiting, and neurological complaints. Additionally, an extreme phenotypic heterogeneity has been reported in AIP patients with mutations in HMBS gene. Here, we investigated a Chinese patient with AIP. The proband is a 28-year-old Chinese male manifested with severe stomach ache, constipation, nausea and depression. Proband’s father and mother is normal. Proband’s blood sample was collected and genomic DNA was extracted. Whole exome sequencing and Sanger sequencing identified a heterozygous novel single nucleotide deletion (c.809delC) in exon 12 of HMBS gene in the proband. This mutation leads to frameshift followed by formation of a truncated (p.Ala270Valfs∗2) HMBS protein with 272 amino acids comparing with the wild type HMBS protein of 361 amino acids. This mutation has not been found in proband’s unaffected parents as well as in 100 healthy normal control. According to the variant interpretation guidelines of American College of Medical Genetics and Genomics (ACMG), this variant is classified as “likely pathogenic” variant. Our findings expand the mutational spectra of HMBS gene related AIP which are significant for screening and genetic diagnosis for AIP.http://journal.frontiersin.org/article/10.3389/fgene.2018.00129/fullacute intermittent porphyriaHMBS geneheme biosynthetic enzymenovel mutationheterozygous |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Yongjiang Zheng Jiehua Xu Shengran Liang Dongjun Lin Santasree Banerjee |
| spellingShingle |
Yongjiang Zheng Jiehua Xu Shengran Liang Dongjun Lin Santasree Banerjee 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 Frontiers in Genetics acute intermittent porphyria HMBS gene heme biosynthetic enzyme novel mutation heterozygous |
| author_facet |
Yongjiang Zheng Jiehua Xu Shengran Liang Dongjun Lin Santasree Banerjee |
| author_sort |
Yongjiang Zheng |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Genetics |
| issn |
1664-8021 |
| publishDate |
2018-04-01 |
| description |
Acute intermittent porphyria (AIP) is a rare hereditary metabolic disease with an autosomal dominant mode of inheritance. Germline mutations of HMBS gene causes AIP. Mutation of HMBS gene results into the partial deficiency of the heme biosynthetic enzyme hydroxymethylbilane synthase. AIP is clinically manifested with abdominal pain, vomiting, and neurological complaints. Additionally, an extreme phenotypic heterogeneity has been reported in AIP patients with mutations in HMBS gene. Here, we investigated a Chinese patient with AIP. The proband is a 28-year-old Chinese male manifested with severe stomach ache, constipation, nausea and depression. Proband’s father and mother is normal. Proband’s blood sample was collected and genomic DNA was extracted. Whole exome sequencing and Sanger sequencing identified a heterozygous novel single nucleotide deletion (c.809delC) in exon 12 of HMBS gene in the proband. This mutation leads to frameshift followed by formation of a truncated (p.Ala270Valfs∗2) HMBS protein with 272 amino acids comparing with the wild type HMBS protein of 361 amino acids. This mutation has not been found in proband’s unaffected parents as well as in 100 healthy normal control. According to the variant interpretation guidelines of American College of Medical Genetics and Genomics (ACMG), this variant is classified as “likely pathogenic” variant. Our findings expand the mutational spectra of HMBS gene related AIP which are significant for screening and genetic diagnosis for AIP. |
| topic |
acute intermittent porphyria HMBS gene heme biosynthetic enzyme novel mutation heterozygous |
| url |
http://journal.frontiersin.org/article/10.3389/fgene.2018.00129/full |
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