The patient is a 10-month and 21-day-old girl who began to show developmental delays at 3 months of age, with severe language developmental disorders, stereotyped movements, and easily provoked laughter. Physical examination revealed fair skin and a flattened occiput. At 10 months of age, a video electroencephalogram suggested atypical absence seizures, with migrating slow-wave activity observed during the interictal period. Whole exome sequencing of three family members indicated a novel mutation in the AP2M1 gene, c.508C>T (p.R170W), in the patient. A total of six cases of autosomal dominant intellectual developmental disorder 60 with seizures associated with mutations in the AP2M1 gene have been reported both domestically and internationally (including this study). The main clinical features included developmental delays (6 cases), language developmental disorders (5 cases), stereotyped movements (3 cases), a tendency to smile (1 case), and atypical absence seizures (4 cases). Interictal electroencephalograms showed widespread spike waves and spike-slow wave discharges (5 cases), and migrating slow-wave activity (1 case). The c.508C>T (p.R170W) mutation may be a hotspot for mutations in the AP2M1 gene, and its clinical features are similar to those of Angelman syndrome.
Key words
Autosomal dominant intellectual developmental disorder 60 with seizures /
Angelman syndrome /
AP2M1 gene /
Child
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References
1 Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. PMID: 25741868. PMCID: PMC4544753. DOI: 10.1038/gim.2015.30.
2 Kelly BT, Graham SC, Liska N, et al. Clathrin adaptors. AP2 controls clathrin polymerization with a membrane-activated switch[J]. Science, 2014, 345(6195): 459-463. PMID: 25061211. PMCID: PMC4333214. DOI: 10.1126/science.1254836.
3 Saheki Y, De Camilli P. Synaptic vesicle endocytosis[J]. Cold Spring Harb Perspect Biol, 2012, 4(9): a005645. PMID: 22763746. PMCID: PMC3428771. DOI: 10.1101/cshperspect.a005645.
4 Dittman J, Ryan TA. Molecular circuitry of endocytosis at nerve terminals[J]. Annu Rev Cell Dev Biol, 2009, 25: 133-160. PMID: 19575674. DOI: 10.1146/annurev.cellbio.042308.113302.
5 Ricotta D, Conner SD, Schmid SL, et al. Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals[J]. J Cell Biol, 2002, 156(5): 791-795. PMID: 11877457. PMCID: PMC2173304. DOI: 10.1083/jcb.200111068.
6 Helbig I, Lopez-Hernandez T, Shor O, et al. A recurrent missense variant in AP2M1 impairs clathrin-mediated endocytosis and causes developmental and epileptic encephalopathy[J]. Am J Hum Genet, 2019, 104(6): 1060-1072. PMID: 31104773. PMCID: PMC6556875. DOI: 10.1016/j.ajhg.2019.04.001.
7 Lek M, Karczewski KJ, Minikel EV, et al. Analysis of protein-coding genetic variation in 60,706 humans[J]. Nature, 2016, 536(7616): 285-291. PMID: 27535533. PMCID: PMC5018207. DOI: 10.1038/nature19057.
8 Mitsunari T, Nakatsu F, Shioda N, et al. Clathrin adaptor AP-2 is essential for early embryonal development[J]. Mol Cell Biol, 2005, 25(21): 9318-9323. PMID: 16227583. PMCID: PMC1265839. DOI: 10.1128/MCB.25.21.9318-9323.2005.
9 王丽, 段丽芬, 边成, 等. 1例AP2M1基因突变致智力发育障碍伴癫痫发作的遗传特征与临床表型分析[J]. 中国优生与遗传杂志, 2023, 31(6): 1241-1245. DOI: 10.13404/j.cnki.cjbhh.2023.06.014.
10 杜晓南, 王佶, 王艺. Angelman综合征的诊断与治疗[J]. 中华儿科杂志, 2023, 61(7): 667-669. PMID: 37385816. DOI: 10.3760/cma.j.cn112140-20230322-00198.
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