Molecular Epidemiologic Study of Citrin Deficiency by Screening for Four Reported Pathogenic SLC25A13 Variants in the Shaanxi and Guangdong Provinces, China

Background: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China.

Methods: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent mutations NG_012247.2 (NM_014251.3): c.852_855del, c.1638_1660dup, c.615+5G>A, and c.1751-5_1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests.

Results: The mutations were detected in 68 out of 6,818 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated allele (68/6,818 29/5,492, χ=8.570, P=0.003) in general, with higher c.852_855del (54/6,818 13/5,492, χ=17.328, P=0.000) but lower c.1751-5_1751 -4ins(2684) (2/6,818 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638_1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly.

Conclusions: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China.