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Clinical and molecular analysis of 6 Chinese patients with isoleucine metabolism defects: identification of 3 novel mutations in the HSD17B10 and ACAT1 gene.
Metab Brain Dis 2017; 32(6):2063-2071MB

Abstract

Hydroxysteroid (17β) dehydrogenase 10 (HSD10) and mitochondrial acetoacetyl-CoA thiolase (β-KT) are two adjacent enzymes for the degradation of isoleucine, thus HSD10 and β-KT deficiencies are confusing at an early stage because of nearly the same elevation of typical metabolites in urine, such as 2-methyl-3-hydroxybutyric acid (2M3HBA) and tiglylglycine (TG). In order to better understand the differences between these two disorders, we described the clinical and molecular characteristics of two HSD10 deficiency patients and four β-KT deficiency patients. β-KT deficiency patients had a much more favorable outcome than that of HSD10 deficiency patients, indicating that the multifunction of HSD10, especially neurosteroid metabolic activity, other than only enzymatic degradation of isoleucine, is involved in the pathogenesis of HSD10 deficiency. Two different mutations, a novel mutation p.Ile175Met and a reported mutation p.Arg226Gln, were detected in the HSD17B10 gene of HSD10 deficiency patients. Six different mutations, including four known mutations: p.Ala333Pro, p.Thr297Lys, c.83_84delAT, c.1006-1G > C, and two novel mutations: p.Thr277Pro and c.121-3C > G were identified in the ACAT1 gene of β-KT deficiency patients. In general, DNA diagnosis played an important role in distinguishing between these two disorders.

Authors+Show Affiliations

Southern Medical University, Guangzhou, 510515, China.Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, China.Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, China.Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, China.Southern Medical University, Guangzhou, 510515, China. fengzc06@126.com. Department of Neonatology, Affiliated Bayi Children's Hospital, Clinical Medical College in PLA Army General Hospital, Southern Medical University, Beijing, 100007, China. fengzc06@126.com.Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, China. liliuxia2010@foxmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28875337

Citation

Su, Ling, et al. "Clinical and Molecular Analysis of 6 Chinese Patients With Isoleucine Metabolism Defects: Identification of 3 Novel Mutations in the HSD17B10 and ACAT1 Gene." Metabolic Brain Disease, vol. 32, no. 6, 2017, pp. 2063-2071.
Su L, Li X, Lin R, et al. Clinical and molecular analysis of 6 Chinese patients with isoleucine metabolism defects: identification of 3 novel mutations in the HSD17B10 and ACAT1 gene. Metab Brain Dis. 2017;32(6):2063-2071.
Su, L., Li, X., Lin, R., Sheng, H., Feng, Z., & Liu, L. (2017). Clinical and molecular analysis of 6 Chinese patients with isoleucine metabolism defects: identification of 3 novel mutations in the HSD17B10 and ACAT1 gene. Metabolic Brain Disease, 32(6), pp. 2063-2071. doi:10.1007/s11011-017-0097-y.
Su L, et al. Clinical and Molecular Analysis of 6 Chinese Patients With Isoleucine Metabolism Defects: Identification of 3 Novel Mutations in the HSD17B10 and ACAT1 Gene. Metab Brain Dis. 2017;32(6):2063-2071. PubMed PMID: 28875337.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and molecular analysis of 6 Chinese patients with isoleucine metabolism defects: identification of 3 novel mutations in the HSD17B10 and ACAT1 gene. AU - Su,Ling, AU - Li,Xiuzhen, AU - Lin,Ruizhu, AU - Sheng,Huiying, AU - Feng,Zhichun, AU - Liu,Li, Y1 - 2017/09/05/ PY - 2017/05/20/received PY - 2017/08/16/accepted PY - 2017/9/7/pubmed PY - 2018/7/4/medline PY - 2017/9/7/entrez KW - Acetoacetyl-CoA thiolase (β-KT) KW - Hydroxysteroid (17β) dehydrogenase 10 (HSD10) KW - Isoleucine metabolism KW - Mutation SP - 2063 EP - 2071 JF - Metabolic brain disease JO - Metab Brain Dis VL - 32 IS - 6 N2 - Hydroxysteroid (17β) dehydrogenase 10 (HSD10) and mitochondrial acetoacetyl-CoA thiolase (β-KT) are two adjacent enzymes for the degradation of isoleucine, thus HSD10 and β-KT deficiencies are confusing at an early stage because of nearly the same elevation of typical metabolites in urine, such as 2-methyl-3-hydroxybutyric acid (2M3HBA) and tiglylglycine (TG). In order to better understand the differences between these two disorders, we described the clinical and molecular characteristics of two HSD10 deficiency patients and four β-KT deficiency patients. β-KT deficiency patients had a much more favorable outcome than that of HSD10 deficiency patients, indicating that the multifunction of HSD10, especially neurosteroid metabolic activity, other than only enzymatic degradation of isoleucine, is involved in the pathogenesis of HSD10 deficiency. Two different mutations, a novel mutation p.Ile175Met and a reported mutation p.Arg226Gln, were detected in the HSD17B10 gene of HSD10 deficiency patients. Six different mutations, including four known mutations: p.Ala333Pro, p.Thr297Lys, c.83_84delAT, c.1006-1G > C, and two novel mutations: p.Thr277Pro and c.121-3C > G were identified in the ACAT1 gene of β-KT deficiency patients. In general, DNA diagnosis played an important role in distinguishing between these two disorders. SN - 1573-7365 UR - https://www.unboundmedicine.com/medline/citation/28875337/Clinical_and_molecular_analysis_of_6_Chinese_patients_with_isoleucine_metabolism_defects:_identification_of_3_novel_mutations_in_the_HSD17B10_and_ACAT1_gene_ L2 - https://doi.org/10.1007/s11011-017-0097-y DB - PRIME DP - Unbound Medicine ER -