論文 - 詳細
| RRC ID | 77049 |
|---|---|
| 著者 | Polla DL, Farazi Fard MA, Tabatabaei Z, Habibzadeh P, Levchenko OA, Nikuei P, Makrythanasis P, Hussain M, von Hardenberg S, Zeinali S, Fallah MS, Schuurs-Hoeijmakers JHM, Shahzad M, Fatima F, Fatima N, Kaat LD, Bruggenwirth HT, Fleming LR, Condie J, Ploski R, Pollak A, Pilch J, Demina NA, Chukhrova AL, Sergeeva VS, Venselaar H, Masri AT, Hamamy H, Santoni FA, Linda K, Ahmed ZM, Nadif Kasri N, de Brouwer APM, Bergmann AK, Hethey S, Yavarian M, Ansar M, Riazuddin S, Riazuddin S, Silawi M, Ruggeri G, Pirozzi F, Eftekhar E, Taghipour Sheshdeh A, Bahramjahan S, Mirzaa GM, Lavrov AV, Antonarakis SE, Faghihi MA, van Bokhoven H. |
| タイトル | Biallelic variants in TMEM222 cause a new autosomal recessive neurodevelopmental disorder. |
| ジャーナル | Genet Med |
| Abstract |
PURPOSE:To elucidate the novel molecular cause in families with a new autosomal recessive neurodevelopmental disorder. METHODS:A combination of exome sequencing and gene matching tools was used to identify pathogenic variants in 17 individuals. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and subcellular localization studies were used to characterize gene expression profile and localization. RESULTS:Biallelic variants in the TMEM222 gene were identified in 17 individuals from nine unrelated families, presenting with intellectual disability and variable other features, such as aggressive behavior, shy character, body tremors, decreased muscle mass in the lower extremities, and mild hypotonia. We found relatively high TMEM222 expression levels in the human brain, especially in the parietal and occipital cortex. Additionally, subcellular localization analysis in human neurons derived from induced pluripotent stem cells (iPSCs) revealed that TMEM222 localizes to early endosomes in the synapses of mature iPSC-derived neurons. CONCLUSION:Our findings support a role for TMEM222 in brain development and function and adds variants in the gene TMEM222 as a novel underlying cause of an autosomal recessive neurodevelopmental disorder. |
| 巻・号 | 23(7) |
| ページ | 1246-1254 |
| 公開日 | 2021-7-1 |
| DOI | 10.1038/s41436-021-01133-w |
| PII | S1098-3600(21)05037-1 |
| PMID | 33824500 |
| PMC | PMC8725574 |
| MeSH | Exome Sequencing Humans Intellectual Disability* / genetics Neurodevelopmental Disorders* / genetics Pedigree |
| リソース情報 | |
| ヒト・動物細胞 | 409B2(HPS0076) |