Identified: Variant of UBE3A Linked to Disease in Six Family Members
In a groundbreaking study published in the journal Molecular Genetics & Genomic Medicine, researchers at The First Affiliated Hospital of Zhengzhou University in China have identified a previously unreported variant in the UBE3A gene that causes Angelman syndrome in six members of a Chinese family.
The initial case involved a 3-year-old girl who was referred to the hospital due to developmental delays and intellectual disabilities. She was the second child of healthy parents, and her birth was uneventful. The girl was hyperflexible in the lower legs, drooled often, showed attention deficits, and had excessive laughter, but had no history of seizures or sleep disorders. Her non-verbal communication abilities were more advanced than her verbal skills, and she only spoke two words: "BaBa" and "MaMa".
The girl's 8-year-old brother was also diagnosed with Angelman syndrome. He had developmental delays with speech impairment, needed help getting dressed, and could only feed himself using a spoon. He had a crossed right eye and was hyperflexible, but he did have a sleep disorder.
The family was screened over three generations, and four members were unaffected carriers of the novel UBE3A variant c.2029G>C. Five other family members had the variant and were also diagnosed with Angelman syndrome.
Angelman syndrome is caused by mutations in the UBE3A gene, leading to the absence or malfunction of the encoded enzyme called ubiquitin-protein ligase E3A in the nervous system. A deficiency in this enzyme results in developmental delays, intellectual disability, abnormal facial features, uncoordinated movements, or seizures, typically beginning in the first year of life.
The variant c.2029G>C was found to alter a critical and stable region of the encoded ubiquitin-protein ligase E3A enzyme, predicted to cause disease. The finding supports genetic counseling for those affected by Angelman syndrome.
Over 250 UBE3A variants are associated with Angelman syndrome, most of which occur sporadically during the early stages of fetal development. In rare cases, variants can be inherited within families, as was the case with this Chinese family.
The researchers who identified a previously unreported variant in the UBE3A gene causing an inherited form of Angelman syndrome in a Chinese family have not been explicitly named in the provided search results. The study expands the genetic spectrum of Angelman syndrome and provides important information for genetic counseling.
