Germline mosaicism for an alanine to valine substitution at residue beta 140 in hemoglobin Puttelange, a new variant with high oxygen affinity
| Autor: | J. Lonsdorfer, E. Lampert, Frédéric Galactéros, Henri Wajcman, Jean Kister, Michel Goossens, M. L. North, François Plassa, J. P. Bergerat, Danielle Promé, F. Oberling, I. Duwig, Emmanuelle Girodon |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Adult
Genetic Markers Male Macromolecular Substances Hemoglobins Abnormal Molecular Sequence Data Germline mosaicism Polycythemia Biology medicine.disease_cause Germline Fathers Genomic Imprinting Germline mutation Valine Genetics medicine Humans Point Mutation Globin Amino Acid Sequence Genetics (clinical) Aged Alanine Mutation Polymorphism Genetic Mosaicism Genetic Variation Middle Aged Molecular biology Peptide Fragments Globins Pedigree Oxyhemoglobins Female Hemoglobin |
| Zdroj: | Human genetics. 96(6) |
| ISSN: | 0340-6717 |
| Popis: | Hb Puttelange [beta 140(H18)Ala--Val] was found as a de novo mutation in two siblings of a French family suffering from polycythemia. Both parents were phenotypically normal and exclusion of paternity has been ruled out by the study of several polymorphic markers located on different chromosomes. The structural modification of Hb Puttelange was established by reversed-phase HPLC analysis of the tryptic digest of the abnormal chain. The amino acid composition of an abnormal beta T14 peptide revealed that one of the four residues of Ala was replaced by a Val. Tandem mass spectrometry demonstrated that the substitution concerned position beta 140 (H18). This hemoglobin displays an increased oxygen affinity that is responsible for the polycythemia. De novo mutations, as demonstrated again in the case of this variant, have the highest probabilities of detection when they lead to pathological manifestations. They may result either from a somatic mutation in a very early stage of the embryological development of the propositus or may have a parental origin with occurrence of a germline mosaicism. The study of the beta-globin gene indicated that this case of Hb Puttelange probably arose from a mutation affecting a part of the germline of the father, therefore leading to a true recurrence risk. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink