Title |
GNAO1 encephalopathy: further delineation of a severe neurodevelopmental syndrome affecting females
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Published in |
Orphanet Journal of Rare Diseases, April 2016
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DOI | 10.1186/s13023-016-0416-0 |
Pubmed ID | |
Authors |
Anna Marcé-Grau, James Dalton, Javier López-Pisón, María Concepción García-Jiménez, Lorena Monge-Galindo, Ester Cuenca-León, Jesús Giraldo, Alfons Macaya |
Abstract |
De novo heterozygous mutations in the GNAO1 gene, encoding the Gα o subunit of G-proteins, are the cause of a severe neurodevelopmental disorder, featuring early infantile seizures, profound cognitive dysfunction and, occasionally, movement disorder (early infantile epileptic encephalopathy-17). We report a further case of this association in a 20 month-old Spanish girl with neonatal-onset refractory seizures, progressive microcephaly, oral-lingual dyskinesia and nearly absent psychomotor development. We performed whole-exome sequencing, a computational structural analysis of the novel gene variant identified and reviewed the previously reported cases. Trio whole-exome-sequencing uncovered a de novo p.Leu199Pro GNAO1 mutation. Computational structural analysis indicates this novel variant adversely affects the stability of the G-protein heterotrimeric complex as a whole. Of note, our patient showed a sustained seizure reduction while on a ketogenic diet. With this observation, a total of twelve patients with GNAO1 encephalopathy have been reported. Oral-lingual dyskinesia and responsiveness of seizures to ketogenic diet are novel features. The distorted sex ratio (12/12 females) of the condition remains unexplained; a differential gender effect of the disruption of G-protein- mediated signal transduction on the developing brain can be hypothesized. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 3 | 30% |
United States | 1 | 10% |
Nigeria | 1 | 10% |
Saudi Arabia | 1 | 10% |
Spain | 1 | 10% |
Unknown | 3 | 30% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 50% |
Scientists | 2 | 20% |
Practitioners (doctors, other healthcare professionals) | 2 | 20% |
Science communicators (journalists, bloggers, editors) | 1 | 10% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 70 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 14 | 20% |
Student > Master | 10 | 14% |
Student > Bachelor | 7 | 10% |
Student > Ph. D. Student | 6 | 9% |
Other | 5 | 7% |
Other | 12 | 17% |
Unknown | 16 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 19 | 27% |
Biochemistry, Genetics and Molecular Biology | 10 | 14% |
Neuroscience | 10 | 14% |
Agricultural and Biological Sciences | 5 | 7% |
Nursing and Health Professions | 2 | 3% |
Other | 3 | 4% |
Unknown | 21 | 30% |