%0 Case Reports
%T Clinical, biochemical, and genetic analysis of a Chinese Han pedigree with holocarboxylase synthetase deficiency: a case report.
%A Zheng Z
%A Yuan G
%A Zheng M
%A Lin Y
%A Zheng F
%A Jiang M
%A Zhu L
%A Fu Q
%J BMC Med Genet
%V 21
%N 1
%D 07 2020 29
%M 32727382
%F 2.023
%R 10.1186/s12881-020-01080-4
%X 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.<BR>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.<BR>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.