title: Novel compound heterozygous mutations in AMN cause Imerslund-Gräsbeck syndrome in two half-sisters: a case report.
abstract: BACKGROUND
  Imerslund-Gräsbeck 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  We have identified novel compound heterozygous mutations in AMN in a family from the United Kingdom with clinical features of Imerslund-Gräsbeck Syndrome.
authors.affiliation: Renal Services Centre, Freeman Hospital, Newcastle upon Tyne NHS Hospitals Foundation Trust Newcastle upon Tyne, Newcastle upon Tyne, NE7 7DN, UK. Emma.Montgomery@nuth.nhs.uk.
authors.forename: Emma
authors.initials: E
authors.lastname: Montgomery
authors.affiliation: Renal Services Centre, Freeman Hospital, Newcastle upon Tyne NHS Hospitals Foundation Trust Newcastle upon Tyne, Newcastle upon Tyne, NE7 7DN, UK. john.sayer@newcastle.ac.uk.|Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne, UK. john.sayer@newcastle.ac.uk.
authors.forename: John A
authors.initials: JA
authors.lastname: Sayer
authors.affiliation: Renal Services Centre, Freeman Hospital, Newcastle upon Tyne NHS Hospitals Foundation Trust Newcastle upon Tyne, Newcastle upon Tyne, NE7 7DN, UK. Laura.Baines@nuth.nhs.uk.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Baines
authors.affiliation: Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne, UK. Ann.Hynes@ncl.ac.uk.
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Hynes
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA. vvegaw@med.umich.edu.
authors.forename: Virginia
authors.initials: V
authors.lastname: Vega-Warner
authors.affiliation: Paediatric Nephrology, Royal Victoria Infirmary, Newcastle upon Tyne NHS Hospitals Foundation Trust, Newcastle upon Tyne, N1 4LP, UK. Sally.Johnson@nuth.nhs.uk.
authors.forename: Sally
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne, UK. Judith.Goddship@nuth.nhs.uk.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Goodship
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA. eotto@med.umich.edu.
authors.forename: Edgar A
authors.initials: EA
authors.lastname: Otto
mesh_terms: D000328:Adult; D000749:Anemia, Megaloblastic; D005260:Female; D006579:Heterozygote; D006801:Humans; D008286:Malabsorption Syndromes / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D010375:Pedigree; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics*; D035781:Siblings; D014806:Vitamin B 12 Deficiency / Q000235:genetics*
chemical_list: C484714:AMN protein, human; D008565:Membrane Proteins; D011506:Proteins