Hb Cervantes, Hb Marañón, Hb La Mancha and Hb Goya: Description of 4 new haemoglobinopathies.
OBJECTIVE
α-thalassemias are caused by a deficiency in or absence of synthesis of the α-chain of haemoglobin (Hb). In contrast, structural haemoglobinopathies are due to mutations that change the amino acid sequence of the protein chain. We report 4 newly identified α-chain Hb variants. Two variants were hyper-unstable, whereas the other 2 were structural variants with an altered electrophoretic mobility.


METHODS
The first 2 families were identified because of microcytosis and hypochromia with a normal Hb A2 and Hb F but without iron deficiency. The other 2 families came to scrutiny because of a peak of abnormal Hb during routine analytical assays. These Hb variants were characterized by specific sequencing.


RESULTS
The hyper-instability of Hb Cervantes is probably due to its lower affinity for the alpha chain haemoglobin-stabilizing protein (AHSP). Hb Marañón is another unstable Hb variant that produces an α-thalassemia phenotype. For the identification of Hb La Mancha, a molecular characterization by sequencing was required. Finally, Hb Goya was found to have the same electrophoretic mobility as Hb J. A lower percentage of the variant was obtained due to a possible component of instability, though the patient did not show evidence of anaemia.


CONCLUSIONS
These variants of Hb add to the variety and complexity of disorders of the genes that encode Hb.
Servicio de Hematología, Hospital Clínico San Carlos de Madrid, Madrid, Spain. Electronic address: felixfuenteg@hotmail.com.
Félix
F
de la Fuente-Gonzalo
Servicio de Hematología, Hospital Clínico San Carlos de Madrid, Madrid, Spain.
Jorge M
JM
Nieto
Servicio de Hematología, Hospital Fundación de Alcorcón, Madrid, Spain.
Pilar
P
Ricard
Servicio de Oncología Infantil, Hospital Universitario Gregorio Marañón, Madrid, Spain.
Javier
J
Anguita
Servicio de Análisis Clínicos, Complejo Hospitalario de Albacete, Albacete, Spain.
Rosalina
R
Martínez
Servicio de Pediatría, Hospital Universitario de Móstoles, Madrid, Spain.
Aurea
A
Cervera
Servicio de Hematología, Hospital Clínico San Carlos de Madrid, Madrid, Spain.
Ana
A
Villegas
Servicio de Hematología, Hospital Clínico San Carlos de Madrid, Madrid, Spain.
Fernando A
FA
González
Servicio de Hematología, Hospital Clínico San Carlos de Madrid, Madrid, Spain.
Paloma
P
Ropero
D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006453:Hemoglobinopathies / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D006455:Hemoglobins, Abnormal
Alpha-thalassemia; Anaemia; Capillary zone electrophoresis; Ion exchange HPLC; Reverse phase HPLC; Sequencing; Structural haemoglobinopathy