Screening for Five Prevalent Mutations of SLC25A13 Gene in Guangdong, China: A Molecular Epidemiologic Survey of Citrin Deficiency

Screening for Five Prevalent Mutations of SLC25A13 Gene in Guangdong, China: A Molecular Epidemiologic Survey of Citrin Deficiency

ZHAN-HUI ZHANG,^1,2 ZHI-GANG YANG,¹ FENG-PING CHEN,³ ATSUO KIKUCHI,⁴ ZHEN-HUAN LIU,⁵ LI-ZHEN KUANG,⁶ WEI-MING LI,⁷ YUAN-ZONG SONG,¹ SHIGEO KURE⁴ and TAKEYORI SAHEKI⁸

¹Department of Pediatrics, The First Afliated Hospital, Jinan University, Guangzhou, Guangdong, P.R. China
²Central Laboratory, The First Afliated Hospital, Jinan University, Guangzhou, Guangdong, P.R. China
³Department of Laboratory Science, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, P.R. China
⁴Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
⁵Department of Pediatric Neurorehabilitation, Nanhai Maternity and Child Care Hospital, Guangzhou University of Chinese Medicine, Foshan, Guangdong, P.R. China
⁶Department of Laboratory Science, Nanhai Maternity and Child Care Hospital, Guangzhou University of Chinese Medicine, Foshan, Guangdong, P.R. China
⁷Department of Pediatrics, Maternal and Child Health Hospital of Qingyuan City, Qingyuan, Guangdong, P.R. China
⁸Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Kumamoto, Japan

Citrin is the liver-type aspartate/glutamate carrier isoform 2 (AGC2) encoded by SLC25A13 gene, playing important roles in the urea cycle and the malate-aspartate shuttle. Citrin deficiency (CD) has proven a disease entity with high prevalence in south China, including Guangdong with the largest population, but CD epidemiology in this province has not been well characterized. This study aims to screen for five prevalent SLC25A13 mutations, c.851_854del (p.R284fs286X), c.1638_1660dup (p.A554fs570X), c.615+5G>A (p.A206fs212X), IVS16ins3kb (p.A584fs585X) and c.1399C>T (p.R467X), to calculate the mutation carrier rate in Guangdong. A total of 2,428 used blood samples for health examination were collected as the research subjects, including 1,558 from 5 cities in the Pearl River Delta area and the remaining 870 from 4 peripheral cities, and the 5 mutations screened using High Resolution Melting Assay and HybProbe assay. A total of 52 carriers were detected, including 2 carriers of a novel c.1420G>A (p.V474M) mutation that impairs citrin function, as judged by the functional analysis in the yeast system. The carrier rate was higher in Pearl River Delta area than that in the peripheral cities (26/1,558 vs. 26/870, with χ² = 4.639 and P < 0.05). The carrier rate was around 1/47 (52/2,428), theoretically with the CD morbidity of 1/8,800 and the number of CD patients over 11,800 in Guangdong population. This study has provided primary epidemiologic data for the evaluation of CD effect in Guangdong province. Moreover, the newly identified c.1420G>A mutation that impairs AGC2 function has enriched the mutation spectrum of human SLC25A13 gene.

keywords —— citrin deficiency; high-frequency mutations; melting curve analysis; mutation; SLC25A13 gene

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Tohoku J. Exp. Med., 2014, 233, 275-281

Correspondence: Yuan-Zong Song, M.D., Ph.D., Department of Pediatrics, The First Afliated Hospital, Jinan University, No. 613 Huangpu Dadao Xi, Tianhe district, Guangzhou, Guangdong 510630, P.R. China.

e-mail: songyuanzong@vip.tom.com