[SLC25A13 gene mutation analysis in a pedigree of neonatal intrahepatic cholestasis caused by citrin deficiency].

Objective: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD, MIM#605814) is an inherited metabolic disease resulting from mutations of the gene SLC25A13, which encodes citrin, a liver-type mitochondrial aspartate-glutamate carrier. Mutation analysis is necessary for definitive diagnosis of NICCD patients. So far (March, 2007), 36 kinds of mutation, including 7 nonsense, 10 missense, 11 abnormal splicing, 4 insertion and 4 deletion, have been identified by Kobayashi's group, who cloned the gene in Kagoshima, Japan. To date, most of the NICCD patients reported in the world are Japanese. This study aimed to explore the gene diagnosis procedure of two known SLC25A13 mutations in a pedigree with an NICCD patient from China.
Methods: DNA was extracted from dried blood spots collected with filter papers from the proband and other 9 members in a NICCD pedigree from China, and then PCR amplification and agarose gel electrophoresis were performed, revealing two mutations preliminarily, which were further proved by Genescan, a procedure established in our laboratory already. Furthermore, the positions and characteristics of the mutations were finally confirmed by DNA sequencing.
Results: The proband is a compound heterozygote of two mutations, 851-854del in exon 9 and 1638-1660dup in exon 16 of SLC25A13 gene. His mother and brother carry the former mutation, which predicts a frameshift and introduction of a stop codon at position 286, while his father, one aunt and her son carry the latter, resulting in a frameshift at codon 554, and introducing a stop codon at position 570.
Conclusion: A deletion mutation 851-854del in exon 9 and an insertion mutation 1638-1660dup in exon 16 of SLC25A13 gene were identified in the pedigree, providing reliable evidences for both diagnostic confirmation of the patient and the genetic counseling from other members in the pedigree.