Prader-Willi and Angelman syndromes are examples of disorders involving imprinted genes. Imprinted genes are only expressed from either the maternally or paternally derived member of a homologous chromosome pair.
Prader-Willi syndrome is characterized by significant infantile hypotonia and feeding difficulties. In early childhood this transitions into excessive eating and morbid obesity. Developmental delay and behavioral problems are common features. Physical characteristics include hypogonadism, short stature, small hands and feet, almond shaped eyes, and hypopigmentation. Prader-Willi syndrome is caused by the lack of expression of the paternally derived region of chromosome 15 (15q11.2-q13). This lack of expression can be caused by a deletion of the paternal chromosome, maternal uniparental disomy (UPD) of chromosome 15 or more rarely, a defect in the imprinting region.
Angelman syndrome is characterized by significant developmental delay or intellectual disability, severe speech impairment, an ataxic gait, and inappropriate happy behavior including excessive laughing and smiling. Other physical concerns include microcephaly, seizures, wide mouth and a prominent mandible. Angelman syndrome is caused by the lack of expression of the maternally inherited region of chromosome 15 (15q11.2-q13). This lack of expression can be caused by a deletion of the maternal chromosome, paternal uniparental disomy (UPD), a mutation in the UBE3 gene in this region, or an imprinting defect.
Southern blot analysis using methylation sensitive restriction enzymes can determine whether the patient has both maternally derived and paternally derived material in the critical region of chromosome 15.