{"doi":"10.1002/ajmg.a.63959","title":"Exploring the Clinical Spectrum of\n                    <scp>\n                      <i>HUWE1</i>\n                    </scp>\n                    ‐Related Neurodevelopmental Disorder: Five New Patients and Literature Review","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>\n                    Turner‐type X‐linked syndromic intellectual developmental disorder (MRXST) is a neurodevelopmental disorder associated with variants in the\n                    <jats:italic>HUWE1</jats:italic>\n                    gene on chromosome Xp11. The condition is characterized by variable phenotypes, including global developmental delay, intellectual disability, and distinctive facial dysmorphisms, with inheritance patterns ranging from X‐linked recessive to de novo mutations in females. Here, we describe five probands in two families, highlighting their clinical features and genetic findings. Trio whole‐exome sequencing identified a de novo variant in\n                    <jats:italic>HUWE1</jats:italic>\n                    in the proband in one family and a maternally inherited hemizygous variant in three boys in a second family. A comprehensive review of\n                    <jats:italic>HUWE1</jats:italic>\n                    ‐associated cases from the literature assisted genotype–phenotype correlations, revealing consistent features such as intellectual disability, skeletal anomalies, and facial dysmorphisms as well as instances of intrafamilial variability. Our findings confirm the phenotypic variability of MRXST and underscore the significance of the\n                    <jats:italic>HUWE1</jats:italic>\n                    gene product in neurodevelopment. We propose a baseline monitoring protocol to aid in diagnosis and management, contributing to the development of specific guidelines for patient follow‐up.\n                  </jats:p>","journal":"American Journal of Medical Genetics Part A","year":2025,"id":599992,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1537945,"name":"Elia Marco Paolo Minale","orcid":"0009-0007-5933-3183","position":1,"is_corresponding":false},{"id":1537946,"name":"Camilla Meossi","orcid":"0000-0002-6574-9608","position":2,"is_corresponding":false},{"id":57184,"name":"Stefano Pagano","orcid":"0009-0009-2456-260X","position":3,"is_corresponding":false},{"id":1537949,"name":"Rosanna Trovato","orcid":"0000-0001-5990-5590","position":4,"is_corresponding":false},{"id":211716,"name":"Emanuele Agolini","orcid":"0000-0001-6543-6225","position":5,"is_corresponding":false},{"id":1396004,"name":"Mafalda Mucciolo","orcid":"0000-0003-2228-8271","position":6,"is_corresponding":false},{"id":296361,"name":"Antonio Novelli","orcid":"0000-0002-9037-4297","position":7,"is_corresponding":false},{"id":241343,"name":"Emanuele Bartolini","orcid":"0000-0002-5683-1941","position":8,"is_corresponding":false},{"id":301282,"name":"Filippo M. Santorelli","orcid":"0000-0002-1359-9062","position":9,"is_corresponding":false},{"id":1537953,"name":"Carmelo Piscopo","orcid":"0009-0009-6117-1974","position":10,"is_corresponding":false},{"id":1537944,"name":"Alessandro De Falco","orcid":"0000-0003-1569-1556","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Exploring the Clinical Spectrum of\n                    <scp>\n                      <i>HUWE1</i>\n                    </scp>\n                    ‐Related Neurodevelopmental Disorder: Five New Patients and Literature Review","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>\n                    Turner‐type X‐linked syndromic intellectual developmental disorder (MRXST) is a neurodevelopmental disorder associated with variants in the\n                    <jats:italic>HUWE1</jats:italic>\n                    gene on chromosome Xp11. The condition is characterized by variable phenotypes, including global developmental delay, intellectual disability, and distinctive facial dysmorphisms, with inheritance patterns ranging from X‐linked recessive to de novo mutations in females. Here, we describe five probands in two families, highlighting their clinical features and genetic findings. Trio whole‐exome sequencing identified a de novo variant in\n                    <jats:italic>HUWE1</jats:italic>\n                    in the proband in one family and a maternally inherited hemizygous variant in three boys in a second family. A comprehensive review of\n                    <jats:italic>HUWE1</jats:italic>\n                    ‐associated cases from the literature assisted genotype–phenotype correlations, revealing consistent features such as intellectual disability, skeletal anomalies, and facial dysmorphisms as well as instances of intrafamilial variability. Our findings confirm the phenotypic variability of MRXST and underscore the significance of the\n                    <jats:italic>HUWE1</jats:italic>\n                    gene product in neurodevelopment. We propose a baseline monitoring protocol to aid in diagnosis and management, contributing to the development of specific guidelines for patient follow‐up.\n                  </jats:p>","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39629746","pmcid":null,"openalex_id":"https://openalex.org/W4405001842","authors":[],"funders":[{"funder_name":"Italian Ministry of Health (Ricerca Corrente 2024)","grant_id":"","title":null}],"total_grants":1,"fwci":2.3547,"citation_percentile":0.89279218,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":3}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.63959","host_type":"publisher"},{"url":"https://doi.org/10.1002/ajmg.a.63959","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39629746","host_type":"repository"}],"fields_of_study":["Genetics and Neurodevelopmental Disorders","Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities","Chromosomal and Genetic Variations","Medicine","Female","Humans","Male","Chromosomes, Human, X","Exome Sequencing","Genetic Association Studies","Intellectual Disability","Mutation","Neurodevelopmental Disorders","Pedigree","Phenotype","Tumor Suppressor Proteins","Ubiquitin-Protein Ligases"],"mesh_terms":["Exome Sequencing","Adolescent","Child","Child, Preschool","Female","Humans","Infant","Male","Intellectual Disability","Mutation","Pedigree","Phenotype","Tumor Suppressor Proteins","Chromosomes, Human, X","Ubiquitin-Protein Ligases","Genetic Association Studies","Neurodevelopmental Disorders"],"keywords":["Proband","Intellectual disability","Genetics","Phenotype","Neurodevelopmental disorder","Exome sequencing","Genetic heterogeneity","Biology","Clinical significance","Genetic counseling","Gene","Medicine","Mutation","Pathology","HUWE1","genotype–phenotype correlation","literature review","turner‐type X‐linked syndromic intellectual developmental disorder"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T11:56:25.428455Z","pmid":null,"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":[]}