{"doi":"10.1002/ajmg.a.63725","title":"Rett syndrome diagnostic odyssey: Limitations of <scp>NextGen</scp> sequencing","abstract":"Typical (or classic) Rett syndrome (RTT) is an X-linked neurodevelopmental disorder characterized by a period of regression, partial or complete loss of purposeful hand movements, and acquired speech, impaired gait, and stereotyped hand movements. In over 95% of typical RTT, a pathogenic variant is found in the methyl-CPG binding protein 2 gene (MECP2). Here, we describe a young woman with clinically diagnosed typical RTT syndrome who lacked a genetic diagnosis despite 20 years of investigation and multiple rounds of sequencing the MECP2 gene. Recently, additional genetic testing using next-generation sequencing was completed, which revealed a partial insertion of the BCL11A gene within exon 4 of MECP2, resulting in a small deletion in MECP2, causing likely disruption of MeCP2 function due to a frameshift. This case demonstrates the ever-changing limitations of genetic testing, as well as the importance of continual pursuit of a diagnosis as technologies improve and are more widely utilized.","journal":"American Journal of Medical Genetics Part A","year":2024,"id":475768,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1313097,"name":"Katie Angione","orcid":null,"position":1,"is_corresponding":false},{"id":1312726,"name":"Emily K. Forbes","orcid":"0000-0003-2372-0126","position":2,"is_corresponding":false},{"id":1313098,"name":"Mikayla Stoecker","orcid":null,"position":3,"is_corresponding":false},{"id":700740,"name":"Margarita Sáenz","orcid":"0000-0002-8782-8059","position":4,"is_corresponding":false},{"id":371111,"name":"Jeffrey L. Neul","orcid":"0000-0002-5628-5872","position":5,"is_corresponding":false},{"id":368521,"name":"Eric D. Marsh","orcid":"0000-0003-3264-0902","position":6,"is_corresponding":false},{"id":311334,"name":"Steven A. Skinner","orcid":"0000-0003-3844-0792","position":7,"is_corresponding":false},{"id":459066,"name":"Alan K. Percy","orcid":"0000-0002-9873-5472","position":8,"is_corresponding":false},{"id":278324,"name":"Tim A. Benke","orcid":"0000-0002-6969-5061","position":9,"is_corresponding":false},{"id":1312725,"name":"Megan Abbott","orcid":"0009-0007-8692-0770","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T02:06:21.071690Z","pmid":"38775384","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}