Hb Nunoi or α₂141(Hc3)Arg → Cysβ₂In A Belgian Female Results From A Cgt →Tgt Mutation In The α2-Globin Gene

Hb Nunobiki [α2 141(HC3) Arg→Cys; HBA2:c.424C>T] in Spain: Mutation de novo or Acquired?

“…The first case reported in Japan, in 1985, probably was a de novo mutation. In the second reported case, the Belgian patient had no known relatives of Japanese descent, and therefore, this Hb would likely be the result of an independent mutation [6,7]. The seven cases reported in Spain were located in the same region (Andalusia), and could all have their origin on the same gene mutation whose involuntary dispersion might be related to a specific event occurred at some point in the distant past.…”

“…The first case of Hb Nunobiki was reported in 1985 on a Japanese male [6]. Eleven years later, a second case was reported on a Belgian woman with no Japanese background, which would suggest an instance of de novo mutation [7]. In this paper, we are reporting 7 cases of Hb Nunobiki found in four families located in the same region in Spain (Andalusia).…”

“…Hb Nunobiki is a variant whose oxygen affinity is increased because the affected amino acid is residue 141 (Arg>Cys) and the COOHterminal arginines of the alpha chains play a major role in normal human hemoglobin (HbA), both by electrostatic interactions which constrain deoxygenated hemoglobin in a low affinity quaternary conformation and by involvement in oxygen-linked anion binding known to give rise to a large part of the alkaline Bohr effect [6]. In spite of this, the cases reported by clinical literature display hematologic parameters that are on the upper limit of normal without pathological implications [6,7]. In this work, we have not been able to perform the functional study of hemoglobin by P 50 determination, but the same behavior has been observed in our patients, whose Hb Nunobiki was detected because it appeared as an interference during Hb A 1c determination (not due to the presence of polyglobulia or abnormal hematological parameters), which reveals that clinically silent hemoglobins can be found while quantifying glycosylated hemoglobin by on-Exchange HPLC.…”

Molecular Characterization of α‐ and β‐Thalassemia Among Children Less Than 18 Years Old in Guizhou, China

“…Additionally, we identified some rare mutations in the Chinese population. One case involved Hemoglobin Nunobiki [Hb Nb, alpha 141 (HC3) Arg → Cys, CGT > TGT] in α‐thalassemia [ 31 ], which did not exhibit a propensity for microcytic hypochromic anemia. Hb Nb was initially detected in a Japanese man, and the proportions of the separated hemoglobin were as follows: Hb Nb 13.1%, Hb A 83.3%, Hb A2 2.6%, and Hb F 0.95%.…”