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Inspissated bile syndrome in an infant with citrin deficiency and congenital anomalies of the biliary tract and esophagus: identification and pathogenicity analysis of a novel SLC25A13 mutation with incomplete penetrance.

Zeng HS, Zhao ST, Deng M, Zhang ZH, Cai XR, Chen FP, Song YZ - Int. J. Mol. Med. (2014)

Bottom Line: The infant had esophageal atresia and an accessory hepatic duct, along with bile plug formation confirmed by laparoscopic surgery.However, the father seemed to be healthy thus far.The findings of the present study enrich the genotypic and phenotypic characteristics of CD patients, and provided clinical and molecular evidence suggesting the possible non-penetrance of SLC25A13 mutations and the likely involvement of this gene in primitive foregut development during early embryonic life.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.

ABSTRACT
Biallelic mutations of the SLC25A13 gene result in citrin deficiency (CD) in humans. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major CD phenotype in pediatrics; however, knowledge on its genotypic and phenotypic characteristics remains limited. The present study aimed to explore novel molecular and clinical characteristics of CD. An infant suspected to have NICCD as well as her parents were enrolled as the research subjects. SLC25A13 mutations were investigated using various methods, including cDNA cloning and sequencing. The pathogenicity of a novel mutation was analyzed bioinformatically and functionally with a yeast model. Both the infant and her father were heterozygous for c.2T>C and c.790G>A, while the mother was only a c.2T>C carrier. The novel c.790G>A mutation proved bioinformatically and functionally pathogenic. The infant had esophageal atresia and an accessory hepatic duct, along with bile plug formation confirmed by laparoscopic surgery. However, the father seemed to be healthy thus far. The findings of the present study enrich the genotypic and phenotypic characteristics of CD patients, and provided clinical and molecular evidence suggesting the possible non-penetrance of SLC25A13 mutations and the likely involvement of this gene in primitive foregut development during early embryonic life.

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SLC25A13 gene variations in the family unveiled by direct DNA sequencing. The patient and her father both harbored the c.2T>C and c.790G>A (p.V264I) variations, while the mother was only a carrier of the former variation.
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f2-ijmm-34-05-1241: SLC25A13 gene variations in the family unveiled by direct DNA sequencing. The patient and her father both harbored the c.2T>C and c.790G>A (p.V264I) variations, while the mother was only a carrier of the former variation.

Mentions: High-frequency mutation screening did not reveal any SLC25A13 mutation. However, direct DNA sequencing revealed that both the infant and her father harbored c.2T>C and c.790G>A (p.V264I) variations, while the mother was only a carrier of c.2T>C (Fig. 2). To the best of our knowledge, c.790G>A is a novel SLC25A13 variation that has not been previously reported. Following SLC25A13 cDNA cloning analysis, from a total of 27 clones from the infant, 7 were found to harbor c.2T>C, another 18 carried c.790G>A, 1 had neither, and the remaining clone had both variations. Analysis of the cDNA clones from the father revealed similar characteristics. The total 29 cDNA clones consisted of 9 clones with c.2T>C, 13 with c.790G>A, 3 with neither, and 4 with both variations. These findings clearly indicated that the 2 variations were both biallelic, not only in the infant displaying clinical characteristics, but also in her father who did not show any symptoms or signs of CD to date.


Inspissated bile syndrome in an infant with citrin deficiency and congenital anomalies of the biliary tract and esophagus: identification and pathogenicity analysis of a novel SLC25A13 mutation with incomplete penetrance.

Zeng HS, Zhao ST, Deng M, Zhang ZH, Cai XR, Chen FP, Song YZ - Int. J. Mol. Med. (2014)

SLC25A13 gene variations in the family unveiled by direct DNA sequencing. The patient and her father both harbored the c.2T>C and c.790G>A (p.V264I) variations, while the mother was only a carrier of the former variation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199400&req=5

f2-ijmm-34-05-1241: SLC25A13 gene variations in the family unveiled by direct DNA sequencing. The patient and her father both harbored the c.2T>C and c.790G>A (p.V264I) variations, while the mother was only a carrier of the former variation.
Mentions: High-frequency mutation screening did not reveal any SLC25A13 mutation. However, direct DNA sequencing revealed that both the infant and her father harbored c.2T>C and c.790G>A (p.V264I) variations, while the mother was only a carrier of c.2T>C (Fig. 2). To the best of our knowledge, c.790G>A is a novel SLC25A13 variation that has not been previously reported. Following SLC25A13 cDNA cloning analysis, from a total of 27 clones from the infant, 7 were found to harbor c.2T>C, another 18 carried c.790G>A, 1 had neither, and the remaining clone had both variations. Analysis of the cDNA clones from the father revealed similar characteristics. The total 29 cDNA clones consisted of 9 clones with c.2T>C, 13 with c.790G>A, 3 with neither, and 4 with both variations. These findings clearly indicated that the 2 variations were both biallelic, not only in the infant displaying clinical characteristics, but also in her father who did not show any symptoms or signs of CD to date.

Bottom Line: The infant had esophageal atresia and an accessory hepatic duct, along with bile plug formation confirmed by laparoscopic surgery.However, the father seemed to be healthy thus far.The findings of the present study enrich the genotypic and phenotypic characteristics of CD patients, and provided clinical and molecular evidence suggesting the possible non-penetrance of SLC25A13 mutations and the likely involvement of this gene in primitive foregut development during early embryonic life.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.

ABSTRACT
Biallelic mutations of the SLC25A13 gene result in citrin deficiency (CD) in humans. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major CD phenotype in pediatrics; however, knowledge on its genotypic and phenotypic characteristics remains limited. The present study aimed to explore novel molecular and clinical characteristics of CD. An infant suspected to have NICCD as well as her parents were enrolled as the research subjects. SLC25A13 mutations were investigated using various methods, including cDNA cloning and sequencing. The pathogenicity of a novel mutation was analyzed bioinformatically and functionally with a yeast model. Both the infant and her father were heterozygous for c.2T>C and c.790G>A, while the mother was only a c.2T>C carrier. The novel c.790G>A mutation proved bioinformatically and functionally pathogenic. The infant had esophageal atresia and an accessory hepatic duct, along with bile plug formation confirmed by laparoscopic surgery. However, the father seemed to be healthy thus far. The findings of the present study enrich the genotypic and phenotypic characteristics of CD patients, and provided clinical and molecular evidence suggesting the possible non-penetrance of SLC25A13 mutations and the likely involvement of this gene in primitive foregut development during early embryonic life.

Show MeSH
Related in: MedlinePlus