Genomic imprinting: genetic mechanisms and phenotypic consequences in Prader-Willi and Angelman syndromes

Abstract

Chromosomal 15q11-q13 region is of great interest in Human Genetics because many structural rearrangements have been described for it (deletions, duplications and translocations) leading to phenotypes resulting in conditions such as the Prader-Willi (PWS) and Angelman (AS) syndromes which were the first human diseases found to be related to the differential expression of parental alleles (genomic imprinting). Contrary to Mendelian laws where the parental inheritance of genetic information does not influence gene expression, genomic imprinting is characterized by DNA modifications that produce different phenotypes depending on the parental origin of the mutation. Clinical manifestation of PWS appears when the loss of paternally expressed genes occurs and AS results from the loss of a maternally expressed gene. Different genetic mechanisms can lead to PWS or AS, such as deletions, uniparental disomy or imprinting mutation. In AS patients an additional class occurs with mutations on the UBE3A gene. Studies of PWS and AS patients can help us to understand the imprinting process, so that other genomic regions with similar characteristics can be located, and different syndromes can have their genetic mechanisms elucidated.

Oral disorders in children with Prader-Willi syndrome: a case control study

“…Therefore, the printing marks the genes in such a way that the origin of the two copies can be distinguished, with one parent's copy being activated and the other's copy silenced [8][9][10]. In the case of PWS, the process depends on the father, there is a fragment of the father's chromosome 15q that is imprinted, that is to say, silenced, and so it is not expressed [9][10][11].…”

Strabismus surgery in Angelman syndrome: More than ocular alignment

“…AS is usually characterized by delayed development, intellectual disability, speech impairment, ataxia, epilepsy and/or abnormal electroencephalography, microcephaly, scoliosis, and a typical behavioural profile, i.e. hyperactivity, an apparently happy demeanour with frequent smiling and laughter [ 8 , 9 ]. As clinical features show wide inter-individual variability, often overlapping with other neuro-behavioural conditions, AS may be difficult to diagnose, especially in the first years of life [ 1 ].…”

Polymorphisms in the SNRPN gene are associated with obesity susceptibility in a Spanish population

“…The small nuclear ribonucleoprotein polypeptide N ( SNRPN ) gene, encoding the RNA‐binding SmN splicing factor involved in RNA processing, is one of the best described genes linked to PWS . The SNRPN gene (15q11.2) includes ten exons that span approximately 155 kb . It is expressed in a tissue‐specific manner, with higher expression levels in the adult brain and heart …”

“…6 The SNRPN gene (15q11.2) includes ten exons that span approximately 155 kb. 7 It is expressed in a tissue-specific manner, with higher expression levels in the adult brain and heart. 8 In the present study, we aimed to assess whether common variants in the SNRPN gene are associated with obesity.…”