Bibliographie

1) Uniparental disomy (UPD) results from the exceptional derivation of a pair of the offspring chromosome from one parent only and has been documented thus far for chromosomes 2, 4, 5, 6, 7, 11, 13, 14, 15, 20, 21, 22 both X's and the XY pair. Its consequences on the phenotype may result from three potentially harmful effects, namely isodisomy, interference with genomic imprinting and, occasionally the vestigial aneuploidy from which UPD may have originated.
2) In isodisomy, the uniparental pair is partially or entirely homozygous, through the duplication of a same chromosomal DNA template, thus bringing about an increased risk of recessive disorders. As a result, conditions such as cystic fibrosis, a type of osteogenesis imperfecta, thalassemia alpha or beta, retinoblastoma, rod monochromacy, etc., have now been reported.
3) Duplication of both homologues of a parental pair in a diploid genome is called heterodisomy. Both iso- and heterodisomy may also cause disruption of the genomic imprints normally modifying the differential expression of some maternal and paternal genes or gene sequences needed for eugenic growth and development, in the course of normal biparental inheritance. Such a disturbance can be one of the causes of congenital clinical entities as well defined as Angelman, Prader-Willi or Beckwith-Wiedemann syndromes and some new syndromes, for instance for UPD 7 mat, UPD 14 mat and, probably also 14 pat.
4) All in all, UPD can cause morbidity or lethality by altering imprinting processes, mimicking certain deletions or duplications, generating recessive disorders or prompting malignant tumor development. 5) In the clinical field, UPD occasionally upsets some mendelian tenets of traditional inheritance, and raises, the question of the evolutional role plaid by genomic imprinting (GI). An hypothetical opinion is that one of GI potential side effects is a biased intergenerational preferential display or skip of parental features. This could be so because some of the inherited genes or gene domains only gain maternal or paternal expression in the offspring, as a function of their parental imprint.

Le syndrome d'Angelman est caractérisé par des accès de rire faciles, une déficience mentale sévère, une ataxie, une absence de langage et une épilepsie presque constante. Il est le plus souvent sporadique mais des récurrences sont possibles. Il peut être associé à une délétion de la région q11-q13 du chromosome 15 d'origine maternelle, ou plus rarement à une disomie paternelle, anomalies présentes dans 60 à 70% des cas. Pour les cas sans délétion ni disomie, qui peuvent comporter des récurrences, les mécanismes moléculaires en cause sont complexes et incomplètement élucidés. L'hétérogénéité génétique de ce syndrome est évidente. Premier exemple en pathologie humaine d'empreinte parentale différentielle, le syndrome d'Angelman est actuellement un des modèles privilégiés d'étude de ses mécanismes moléculaires.

The Angelman syndrome is a neurological disorder characterized by constant features : severe mental retardation, easily provoked laughter, ataxia, absent speech, seizures. Most cases are sporadic but familial cases have been reported. About 60 to 70% of cases are due to an interstitial deletion on the maternally inherited chromosome 15 in the region q11-q13. Rare cases result from paternal disomy. In 30% of patients, neither maternal by inherited deletion, nor paternal disomy, can be found. In this category of patients recurrence risk for sibs is high and molecular mechanisms are not completely known. They appear to be more complex than previously syggested. It is clear that this syndrome is a genetically heterogeneous group. The main example of genomic imprinting in human pathology, Angelman syndrome is now a model in research for understanding molecular mechanisms underlying imprinting.

Par en haut !
This way up !
Retour à la page d'accueil...
Back to Home Page...