TY - JOUR
T1 - Clinical and molecular characteristics of imerslund-gräsbeck syndrome
T2 - First report of a novel Frameshift variant in Exon 11 of AMN gene
AU - Elshinawy, Mohamed
AU - Gao, Harry H.
AU - Al-Nabhani, Dana M.
AU - Al-Thihli, Khalid A.
N1 - Publisher Copyright:
© 2021 John Wiley & Sons Ltd
PY - 2021/10
Y1 - 2021/10
N2 - Introduction: Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal-recessive disorder characterized by selective vitamin B12 malabsorption, megaloblastic anemia, and proteinuria. The precise incidence of this disorder is unknown in the Middle East and Arab countries. The disease is caused by a homozygous variant in either AMN or CUBN genes. In addition, some compound heterozygous variants are reported. Methods: Clinical and laboratory data of patients diagnosed with IGS in Oman were retrospectively collected. Mutation analysis for all genes involved in vitamin B12/folic acid metabolism and megaloblastic anemia was conducted using next-generation sequencing (NGS). Results: Three siblings (2 girls and a boy) have been diagnosed with the condition. They exhibit a phenotypic variability with different age of presentation and different spectrum of disease. All patients harbor a novel biallelic frameshift mutation in exon 11 of AMN gene (p.Pro409Glyfs*), which was not reported previously in the literature. Both parents are heterozygotes for the same variant. All patients responded well to vitamin B12 parenteral therapy, but proteinuria persisted. Conclusion: In communities with high incidence of consanguinity, cases of early-onset vitamin B12 deficiency should be thoroughly investigated to explore the possibility of Imerslund-Gräsbeck syndrome and other vitamin B12–related hereditary disorders. Further local and regional studies are highly recommended.
AB - Introduction: Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal-recessive disorder characterized by selective vitamin B12 malabsorption, megaloblastic anemia, and proteinuria. The precise incidence of this disorder is unknown in the Middle East and Arab countries. The disease is caused by a homozygous variant in either AMN or CUBN genes. In addition, some compound heterozygous variants are reported. Methods: Clinical and laboratory data of patients diagnosed with IGS in Oman were retrospectively collected. Mutation analysis for all genes involved in vitamin B12/folic acid metabolism and megaloblastic anemia was conducted using next-generation sequencing (NGS). Results: Three siblings (2 girls and a boy) have been diagnosed with the condition. They exhibit a phenotypic variability with different age of presentation and different spectrum of disease. All patients harbor a novel biallelic frameshift mutation in exon 11 of AMN gene (p.Pro409Glyfs*), which was not reported previously in the literature. Both parents are heterozygotes for the same variant. All patients responded well to vitamin B12 parenteral therapy, but proteinuria persisted. Conclusion: In communities with high incidence of consanguinity, cases of early-onset vitamin B12 deficiency should be thoroughly investigated to explore the possibility of Imerslund-Gräsbeck syndrome and other vitamin B12–related hereditary disorders. Further local and regional studies are highly recommended.
KW - AMN gene
KW - Imerslund-Gräsbeck syndrome
KW - megaloblastic anemia
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U2 - 10.1111/ijlh.13473
DO - 10.1111/ijlh.13473
M3 - Article
C2 - 33491342
AN - SCOPUS:85099826777
SN - 1751-5521
VL - 43
SP - 1009
EP - 1015
JO - International Journal of Laboratory Hematology
JF - International Journal of Laboratory Hematology
IS - 5
ER -