Infantile Cirrhosis, Growth Impairment, and Neurodevelopmental Anomalies Associated with Deficiency of PPP1R15B

详细信息    查看全文

• 作者：Saeed Mohammad ; MD¹ ; Lynne A. Wolfe ; MS ; CRNP² ; Petra Stö ; be ; PhD³ ; Saskia Biskup ; MD ; PhD³ ; Mark S. Wainwright ; MD ; PhD⁴ ; Hector Melin-Aldana ; MD⁵ ; Padmini Malladi ; MS¹ ; Maximilian Muenke ; MD⁶ ; William A. Gahl ; MD ; PhD⁷ ; Peter F. Whitington ; MD¹
• 关键词：whole exome ; translation initiation factor ; infantile cirrhosis
• 刊名：The Journal of Pediatrics
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：179
• 期：Complete
• 页码：144-149.e2
• 全文大小：1876 K

文摘

To assess the utility of whole-exome sequencing (WES) in a sibling pair with undetermined liver disease and describe the phenotype associated with mutations discovered therein.

Study design

Next-generation WES was performed on 2 siblings (S1 and S2) who were born to nonconsanguineous parents of European extraction. Both siblings developed cirrhosis of indeterminate etiology and required liver transplantation; S1 at 7 months and S2 at 22 months.

Results

Sequencing of germline DNA identified compound heterozygous mutations in PPP1R15B resulting in increased levels of phosphorylated eukaryotic translation initiation factor 2α.

Conclusions

The first demonstration of PPP1R15B associated with liver disease expands the phenotypic spectrum of PPP1R15B related diseases. Our findings validate the application of WES in the diagnosis of children with undetermined liver disease. Understanding the genetic basis of liver disease may allow the development of targeted therapies for treatment and adequate counseling of families.