Hemoglobin Phnom Penh [α117Phe(H1)-Ile-α118Thr(H2)]; evidence for a hotspot for insertion of residues in the third exon of the α1-globin gene

Wajcman, Henri; Prehu, Marie-Odette; Préhu, Claude; Blouquit, Y.; Promé, Danièlle; Galactéros, Frédéric

doi:10.1002/humu.1380110107

Cited by 13 publications

(6 citation statements)

References 8 publications

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“…In agreement with these observations, the most likely hypothesis is that the deletion starts at the beginning of the loop which is found at the end of the first repeated nucleotide sequence. This region may therefore be a hotspot for breakpoints similar to that we have previously described at the beginning of the third exon of the α chain ( Wajcman et al , 1997 ) and we may predict that non‐deletional α‐thalassaemias involving out‐of‐frame deletions starting in this region are likely to be found.…”

Section: Discussionsupporting

confidence: 64%

Haemoglobin J‐Biskra: a new mildly unstable α1 gene variant with a deletion of eight residues (α50–57, α51–58 or α52–59) including the distal histidine

Wajcman

Dahmane²,

Préhu³

et al. 1998

Br J Haematol

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Single point mutation, which accounts for 92% of the 700 known variants, is the most frequent genetic defect responsible for abnormal haemoglobins. Small deletions (or insertions) involving from one to five residues are also observed, but in only approximately 5% of cases. The remaining variants produce fusion or extended haemoglobins. A deletion of eight residues, which included the distal histidine and its neighbours (alpha50-57, alpha51-58 or alpha52-59), was found in Hb J-Biskra. This new alpha-chain variant was mildly unstable in vitro only and there was no haematological or biochemical evidence of haemolysis in the affected family members. 24 nucleotides were missing in a region of the alpha1 gene showing an identical sequence of eight nucleotides at both ends. Several starting points could therefore lead to the same nucleotide and aminoacid remaining sequence. This deletion is the largest up to now reported in a haemoglobin molecule which is expressed at an almost normal level in the red blood cell. Comparison of the DNA sequences near to the deleted (or inserted) regions in the various haemoglobins carrying this type of abnormality almost always revealed the presence of a sequence that was hypothesized to slow down progression of the replication fork, and of repeats that may lead to possible secondary structures favouring slipped mispairing.

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Section: Discussionsupporting

confidence: 64%

Haemoglobin J‐Biskra: a new mildly unstable α1 gene variant with a deletion of eight residues (α50–57, α51–58 or α52–59) including the distal histidine

Wajcman

Dahmane²,

Préhu³

et al. 1998

Br J Haematol

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“…The CID fragments observed for the variant are shown in Supplemental Table 7. The variant was identified as Hb Phnom Penh which arises through insertion of an isoleucine between position 117 and 118 on the α-chain coded by the α 1 gene [34]. The protein sequence coverage was 46 % and is summarised in Figure 4b.…”

Section: Diagnosis Of Unknown Variantsmentioning

confidence: 99%

Top-Down Proteomics and Direct Surface Sampling of Neonatal Dried Blood Spots: Diagnosis of Unknown Hemoglobin Variants

Edwards

Griffiths

Bunch

et al. 2012

J. Am. Soc. Mass Spectrom.

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We have previously shown that liquid microjunction surface sampling of dried blood spots coupled with high resolution top-down mass spectrometry may be used for screening of common hemoglobin variants HbS, HbC, and HbD. In order to test the robustness of the approach, we have applied the approach to unknown hemoglobin variants. Six neonatal dried blood spot samples that had been identified as variants, but which could not be diagnosed by current screening methods, were analyzed by direct surface sampling top-down mass spectrometry. Both collision-induced dissociation and electron transfer dissociation mass spectrometry were employed. Four of the samples were identified as β-chain variants: two were heterozygous Hb D-Iran, one was heterozygous Hb Headington, and one was heterozygous Hb J-Baltimore. The fifth sample was identified as the α-chain variant heterozygous Hb Phnom Penh. Analysis of the sixth sample suggested that it did not in fact contain a variant. Adoption of the approach in the clinic would require speed in both data collection and interpretation. To address that issue, we have compared manual data analysis with freely available data analysis software (ProsightPTM). The results demonstrate the power of top-down proteomics for hemoglobin variant analysis in newborn samples.

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“…Several cases have been reported since then (5-7), but this is the first report from Japan. Most Hb Phnom Penh cases, including the present case, have no hematological abnormalities (5,7). Only one case complicated with α-thalassemia showed microcytic hypochromic anemia (6).…”

Section: Discussionmentioning

confidence: 50%

Hb Phnom Penh Showing Falsely High or Reasonable HbA1c Values Depending on the Type of High-performance Liquid Chromatography System

Hara

Koga²,

Shinozaki

et al. 2020

Intern. Med.

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We herein report a 50-year-old Chinese woman with Hb Phnom Penh (α117Phe-Ile-α118Thr) showing high or reasonable HbA1c values depending on the type of high-performance liquid chromatography (HPLC) system. A high HbA1c value of 7.5% (HPLC assay: G9) and a reasonable HbA1c value of 5.2% (assay unknown) were observed. Therefore, the patient was refereed to our hospital; the oral glucose tolerance test showed normal glucose tolerance. The HbA1c values measured by an enzymatic assay, immunoassay, and affinity assay, as well as most HPLC assays were within the reference range, whereas those measured by the Tosoh HPLC systems were high.

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Hemoglobin Phnom Penh [α117Phe(H1)-Ile-α118Thr(H2)]; evidence for a hotspot for insertion of residues in the third exon of the α1-globin gene

Cited by 13 publications

References 8 publications

Haemoglobin J‐Biskra: a new mildly unstable α1 gene variant with a deletion of eight residues (α50–57, α51–58 or α52–59) including the distal histidine

Haemoglobin J‐Biskra: a new mildly unstable α1 gene variant with a deletion of eight residues (α50–57, α51–58 or α52–59) including the distal histidine

Top-Down Proteomics and Direct Surface Sampling of Neonatal Dried Blood Spots: Diagnosis of Unknown Hemoglobin Variants

Hb Phnom Penh Showing Falsely High or Reasonable HbA1c Values Depending on the Type of High-performance Liquid Chromatography System

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