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In approximately 10\u201320% of cases, they may present with\u00a0muscle weakness and\/or cardiomyopathy. We aimed to describe clinical and molecular characteristics of DMD heterozygous females.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A monocentric, observational, and cross-sectional study was designed. Clinical and molecular data were collected along with, when available, muscle biopsies. The pattern of X inactivation was determined in peripheral blood and the genotypes at <jats:italic>SPP1<\/jats:italic>, <jats:italic>LTBP4<\/jats:italic> and <jats:italic>CD40<\/jats:italic> modifier genes were established.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We recruited 47 participants: 27 (57%) were asymptomatic and 20 (43%) manifested symptoms. Proximal muscles were prominently involved, as in male dystrophinopathies. Twenty % of carriers showed cardiac involvement. Creatine kinase (CK) values were in the normal range in\u2009~\u200920% of symptomatic and\u2009~\u200946% asymptomatic patients. In all muscle biopsies, a mosaic of dystrophin positive and negative fibers was observed that only marginally correlated to dystrophin amount. No correlation was found between X chromosome inactivation pattern and the severity of muscular involvement, nor any association with cardiomyopathy. No genotype\u2013phenotype correlations were identified.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Interpretation<\/jats:title>\n            <jats:p>Genotype\/phenotype correlations in females heterozygous for <jats:italic>DMD<\/jats:italic> mutations are influenced by multiple mechanisms, of which better understanding will be crucial for future dystrophin gene replacement therapies. An earlier molecular identification is essential to lead to greater awareness of the potential cardiac complications, and hence the reinforcement of \u00a0appropriate cardiac follow-up.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-025-12987-4","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T16:04:35Z","timestamp":1741104275000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Deep characterization of females with heterozygous Duchenne muscular dystrophy mutations"],"prefix":"10.1007","volume":"272","author":[{"given":"Pietro","family":"Riguzzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Sabbatini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Fusto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Vianello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Merlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Zangaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Capece","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Gorgoglione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Sorar\u00f9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Bariani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Calore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Bauce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Martini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mutterle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Bello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-4156","authenticated-orcid":false,"given":"Elena","family":"Pegoraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"issue":"5","key":"12987_CR1","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1136\/jmg.15.5.339","volume":"15","author":"AM Davie","year":"1978","unstructured":"Davie AM, Emery AE (1978) Estimation of proportion of new mutants among cases of Duchenne muscular dystrophy. 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Luca Bello acknowledges research support from PTC Therapeutics; payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from PTC Therapeutics and Pfizer; payments for expert testimony from PTC Therapeutics; payments for participation on a Data Safety Monitoring Board or Advisory Board from PTC Therapeutics, Edgewise Therapeutics, and Roche. Gianni Sorar\u00f9 acknowledges research support from ARISLA SYMP-ALS and PNRR-MR1-2022\u201312375938; payments for participation on a Data Safety Monitoring Board or Advisory Board from Advisory Board Zambon Italia SLA and Advisory Board PHARMALEX Italy S.p.A","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Clinical investigations adhered to the Declaration of Helsinki principles, and written informed consent, approved by institutional review boards, was obtained from all participants or their guardians in accordance with ethical requirements. The coordinating center IRB protocol number is 428n\/AO\/23.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standard"}}],"article-number":"244"}}