NDLI: A combination of mutations in AKR1D1 and SKIV2L in a family with severe infantile liver disease

Content Provider	Springer Nature : BioMed Central
Author	Morgan, Neil V Hartley, Jane L Setchell, Kenneth DR Simpson, Michael A Brown, Rachel Tee, Louise Kirkham, Sian Pasha, Shanaz Trembath, Richard C Maher, Eamonn R Gissen, Paul Kelly, Deirdre A
Abstract	Infantile cholestatic diseases can be caused by mutations in a number of genes involved in different hepatocyte molecular pathways. Whilst some of the essential pathways have a well understood function, such as bile biosynthesis and transport, the role of the others is not known. Here we report the findings of a clinical, biochemical and molecular study of a family with three patients affected with a severe infantile cholestatic disease. A novel homozygous frameshift germline mutation (c.587delG) in the AKR1D1 gene; which encodes the enzyme Δ 4-3-oxosteroid 5β–reductase that is required for synthesis of primary bile acids and is crucial for establishment of normal bile flow, was found in all 3 patients. Although the initial bile acid analysis was inconclusive, subsequent testing confirmed the diagnosis of a bile acid biogenesis disorder. An additional novel homozygous frameshift mutation (c.3391delC) was detected in SKIV2L in one of the patients. SKIV2L encodes a homologue of a yeast ski2 protein proposed to be involved in RNA processing and mutations in SKIV2L were recently described in patients with Tricohepatoenteric syndrome (THES). A combination of autozygosity mapping and whole-exome-sequencing allowed the identification of causal mutations in this family with a complex liver phenotype. Although the initial 2 affected cousins died in the first year of life, accurate diagnosis and management of the youngest patient led to successful treatment of the liver disease and disease-free survival.
Related Links	https://ojrd.biomedcentral.com/counter/pdf/10.1186/1750-1172-8-74.pdf
Ending Page	5
Page Count	5
Starting Page	1
File Format	HTM / HTML
ISSN	17501172
DOI	10.1186/1750-1172-8-74
Journal	Orphanet Journal of Rare Diseases
Issue Number	1
Volume Number	8
Language	English
Publisher	BioMed Central
Publisher Date	2013-05-16
Access Restriction	Open
Subject Keyword	Medicine Public Health Pharmacology Toxicology Human Genetics Bile acid metabolism Diarrhoea Gene mutation Whole exome sequencing Paediatric liver disease Medicine/Public Health Pharmacology/Toxicology
Content Type	Text
Subject	Pharmacology (medical) Genetics (clinical)
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.9/2023

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