A New α-Globin Variant with Increased Oxygen Affinity in a Swiss Family: Hb Frauenfeld [α138(H21)Ser→Phe, T<i>C</i>C&gt;T<i>T</i>C (α 2)]

Hochuli, Michel; Zurbriggen, Karin; Schmid, Marlis; Speer, Oliver; Rochat, Philippe; Frauchiger, Beat; Kleinert, P.; Schmugge, Markus; Troxler, Heinz

doi:10.1080/03630260802625733

Cited by 3 publications

(1 citation statement)

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“…Conventionally mutations in proteins are assigned from the sequencing data of DNA. To verify the mutations as predicted from DNA sequences, determining the change in molecular mass of the proteins alone is not sufficient; 34,35 the exact site of mutation in the protein needs to be determined as well. In cases of changes in DNA sequence that correspond to small differences in molecular mass of the protein, there is very limited scope for verifying minute variations at the protein level.…”

Section: Discussionmentioning

confidence: 99%

Identifying N60D mutation in ω subunit of Escherichia coli RNA polymerase by bottom-up proteomic approach

Sabareesh

Sarkar

Sardesai

et al. 2010

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Escherichia coli RNA polymerase is a multi-subunit enzyme containing α(2)ββ'ωσ, which transcribes DNA template to intermediate RNA product in a sequence specific manner. Although most of the subunits are essential for its function, the smallest subunit ω (average molecular mass ∼ 10,105 Da) can be deleted without affecting bacterial growth. Creating a mutant of the ω subunit can aid in improving the understanding of its role. Sequencing of rpoZ gene that codes for ω subunit from a mutant variant suggested a substitution mutation at position 60 of the protein: asparagine (N) → aspartic acid (D). This mutation was verified at the protein level by following a typical mass spectrometry (MS) based bottom-up proteomic approach. Characterization of in-gel trypsin digested samples by reverse phase liquid chromatography (LC) coupled to electrospray ionization (ESI)-tandem mass spectrometry (MS/MS) enabled in ascertaining this mutation. Electron transfer dissociation (ETD) of triply charged [(M + 3H)(3+)] tryptic peptides (residues [53-67]), EIEEGLINNQILDVR from wild-type and EIEEGLIDNQILDVR from mutant, facilitated in unambiguously determining the site of mutation at residue 60.

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Section: Discussionmentioning

confidence: 99%

Identifying N60D mutation in ω subunit of Escherichia coli RNA polymerase by bottom-up proteomic approach

Sabareesh

Sarkar

Sardesai

et al. 2010

Analyst

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Hereditary gene mutations in Korean patients with isolated erythrocytosis

et al. 2014

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Most cases of erythrocytosis occur secondary to chronic tissue hypoxia or as a clonal disease such as polycythemia vera with somatic mutations in the Janus kinase 2 (JAK2) gene. Rarely, erythrocytosis is caused by hereditary gene mutations. This study investigated hereditary gene mutations in 38 unrelated Korean patients with isolated erythrocytosis without (1) JAK2 mutation and (2) secondary causes of erythrocytosis other than smoking history. Direct sequencing analyses were performed on six genes associated with hereditary erythrocytosis [HBB, exon 2 and exon 3 of HBA2, VHL, EGLN1 (previously PHD2), exon 12 of EPAS1 (previously HIF2A), and exons 5-8 of EPOR]. As a result, mutations were detected in five patients (three never smokers and two current smokers) out of 38 patients (13.2 %). The mutations detected in those five patients were EPOR:p.W439*, EPOR:p.G212C, HBB:p.H98Q (or conventionally H97Q, Hb Malmö [β 97(FG4) His > Gln]), HBB:p.V138M (V137M), and EGLN1:p.L279Tfs43*, all in heterozygous state. No patient had mutations in HBA2, VHL, or in EPAS1. This study indicates that workup for hereditary gene mutations is needed for isolated erythrocytosis with or without smoking history.

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