RESUMEN
Hb Kenya is a hemoglobin (Hb) tetramer composed of two normal α- and two non α-globin chains. The latter are the product of a fusion gene in which the 5' end is (A)γ and the 3' end is ß. The crossover point is between codon 81 of the (A)γ gene and codon 86 of the ß gene. Like the other non α genes, the hybrid protein product ((A)γ81Leu-ß86Ala) has 146 amino acids. The purpose of this report is to highlight the laboratory findings of Hb Kenya and to emphasize the pitfalls in misdiagnosis, particularly when associated with another variant such as Hb S [ß6(A3)GluâVal].
Asunto(s)
Hemoglobina Fetal/genética , Hemoglobina Falciforme/genética , Hemoglobinas Anormales/genética , Heterocigoto , Adulto , Análisis Mutacional de ADN , Femenino , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/genética , Humanos , Embarazo , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/genética , UgandaRESUMEN
Hb H disease is rarely seen in individuals of African descent although α-thalassemia (α-thal) is common in this population. Usually α-thal is due either to heterozygosity or homozygosity for the -α(3.7) deletion in this population. We report Hb H disease that is caused by a frameshift mutation on one -α(3.7) allele in two unrelated individuals homozygous for the -α(3.7) deletion. These two cases highlight the importance of further investigation by direct sequencing of the -α(3.7) allele when the thalassemic phenotype does not correlate with the genotype obtained by initial molecular testing.
Asunto(s)
Mutación del Sistema de Lectura , Hemoglobina H/genética , Eliminación de Secuencia , Talasemia alfa/genética , Adolescente , Adulto , Negro o Afroamericano , Secuencia de Bases , Análisis Mutacional de ADN , Femenino , Homocigoto , Humanos , Masculino , Globinas alfa/genéticaRESUMEN
We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.
Asunto(s)
Bases de Datos Genéticas , Variación Genética , Hemoglobinopatías/genética , Secuencia de Bases , ADN/genética , Minería de Datos , Genoma Humano , Hemoglobinas/genética , Proyecto Genoma Humano , Humanos , Datos de Secuencia Molecular , Mutación , Regiones Promotoras Genéticas , EdiciónRESUMEN
We report a novel thalassemia determinant found in a Nigerian woman living in the Netherlands, resulting from a 2 bp insertion at codons 9/10 of the ß-globin gene (HBBc.28_29insTA p.Ser10LeufsX11). The novel defect causes a frameshift with a consequent premature TGA stop codon, located at 11 positions downstream from the mutated codon. The phenotype was typical of a ß-thalassemia (ß-thal), trait with high RBC counts and compensated mild microcytic anemia. However, the Hb A(2) level was reported to be normal due to the presence of the common Hb A(2)' or Hb B2 [δ16(A13)GlyâArg, GGC>CGC] variant that was not taken into account. We also present the opposite but comparable situation found in an a Palestinian man living in the USA. He was a carrier of a common ß-globin gene defect [codon 6 (-A), HBB:c.20delA] in combination with a novel δ-globin gene defect at codon 6 [HBD. c.19G>C, Glu6Gln] that we have named Hb A(2)-Ramallah. In both cases, the provisional diagnosis could have been compromised when based on the measurement of the normal Hb A(2) fraction only.