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Novel compound heterozygous mutations in AMN cause Imerslund-Gräsbeck syndrome in two half-sisters: a case report

Lookup NU author(s): Professor John SayerORCiD, Dr Ann Marie Hynes, Dr Sally Johnson, Professor Judith Goodship



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background: Imerslund-Grasbeck Syndrome (IGS) is a rare autosomal recessive disease characterized by intestinal vitamin B12 malabsorption. Clinical features include megaloblastic anemia, recurrent infections, failure to thrive, and proteinuria. Recessive mutations in cubilin (CUBN) and in amnionless (AMN) have been shown to cause IGS. To date, there are only about 300 cases described worldwide with only 37 different mutations found in CUBN and 30 different in the AMN gene.Case presentation: We collected pedigree structure, clinical data, and DNA samples from 2 Caucasian English half-sisters with IGS. Molecular diagnostics was performed by direct Sanger sequencing of all 62 exons of the CUBN gene and 12 exons of the AMN gene. Because of lack of parental DNA, cloning, and sequencing of multiple plasmid clones was performed to assess the allele of identified mutations. Genetic characterization revealed 2 novel compound heterozygous AMN mutations in both half-sisters with IGS. Trans-configuration of the mutations was confirmed.Conclusion: We have identified novel compound heterozygous mutations in AMN in a family from the United Kingdom with clinical features of Imerslund-Grasbeck Syndrome.

Publication metadata

Author(s): Montgomery E, Sayer JA, Baines LA, Hynes AM, Vega-Warner V, Johnson S, Goodship JA, Otto EA

Publication type: Article

Publication status: Published

Journal: BMC Medical Genetics

Year: 2015

Volume: 16

Online publication date: 04/06/2015

Acceptance date: 29/05/2015

Date deposited: 05/04/2016

ISSN (electronic): 1471-2350

Publisher: BioMed Central Ltd


DOI: 10.1186/s12881-015-0181-2


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