Clinical, biochemical, and genetic analysis of a Chinese Han pedigree with holocarboxylase synthetase deficiency: a case report
| Autor: | Faming Zheng, Yiming Lin, Lin Zhu, Zhenzhu Zheng, Qingliu Fu, Mengyi Jiang, Minyan Zheng, Gaopin Yuan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Proband
Male lcsh:Internal medicine lcsh:QH426-470 Holocarboxylase Synthetase Deficiency 030204 cardiovascular system & hematology Biology Frameshift mutation 03 medical and health sciences symbols.namesake Exon 0302 clinical medicine Asian People Protein Domains Case report Genetics medicine Ethnicity Missense mutation Humans Carbon-Nitrogen Ligases Amino Acid Sequence lcsh:RC31-1245 Genetics (clinical) Holocarboxylase synthetase deficiency Sanger sequencing Base Sequence Hearing damage Infant Arg508Trp medicine.disease Human genetics Pedigree lcsh:Genetics Mutation symbols Metabolome HLCS deficiency Holocarboxylase synthetase Female 030217 neurology & neurosurgery |
| Zdroj: | BMC Medical Genetics, Vol 21, Iss 1, Pp 1-6 (2020) BMC Medical Genetics |
| ISSN: | 1471-2350 |
| DOI: | 10.1186/s12881-020-01080-4 |
| Popis: | Background Holocarboxylase synthetase (HLCS) deficiency is a rare inborn disorder of biotin metabolism, which results in defects in several biotin-dependent carboxylases and presents with metabolic ketoacidosis and skin lesions. Case presentation In this paper, we report a Chinese Han pedigree with HLCS deficiency diagnosed by using next-generation sequencing and validated with Sanger sequencing of the HLCS and BTD genes. The Chinese proband carries the common missense mutation c.1522C > T (p.Arg508Trp) in exon 9 of the HLCS gene, which generates an increased Km value for biotin. A novel frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15) in exon 6 of the HLCS gene is predicted to be deleterious through PROVEAN and MutationTaster. A novel heterozygous mutation, c.638_642delAACAC (p.His213Profs*4), in the BTD gene is also identified. Conclusions The Chinese proband carries the reported Arg508Trp variant, the novel 2-bp frameshift mutation c.1006_1007delGA (p.Glu336Thrfs*15), which expands the mutational spectrum of the HLCS gene, and the novel heterozygous mutation c.638_642delAACAC (p.His213Profs*4), which expands the mutational spectrum of the BTD gene. Furthermore, reversible hearing damage is rarely reported in patients with HLCS deficiency, which deserves further discussion. |
| Databáze: | OpenAIRE |
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