{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:31:20Z","timestamp":1788294680271,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,10,14]],"date-time":"2016-10-14T00:00:00Z","timestamp":1476403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"None"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>Filamin A is an X\u2010linked, ubiquitous actin\u2010binding protein whose mutations are associated to multiple disorders with limited genotype\u2013phenotype correlations. While gain\u2010of\u2010function mutations cause various bone dysplasias, loss\u2010of\u2010function variants are the most common cause of periventricular nodular heterotopias with variable soft connective tissue involvement, as well as X\u2010linked cardiac valvular dystrophy (XCVD). The term \u201cEhlers\u2013Danlos syndrome (EDS) with periventricular heterotopias\u201d has been used in females with neurological, cardiovascular, integument and joint manifestations, but this nosology is still a matter of debate. We report the clinical and molecular update of an Italian family with an X\u2010linked recessive soft connective tissue disorder and which was described, in 1975, as the first example of EDS type V of the Berlin nosology. The cutaneous phenotype of the index patient was close to classical EDS and all males died for a lethal cardiac valvular dystrophy. Whole exome sequencing identified the novel c.1829\u20101G&gt;C splice variation in <jats:italic>FLNA<\/jats:italic> in two affected cousins. The nucleotide change was predicted to abolish the canonical splice acceptor site of exon 13 and to activate a cryptic acceptor site 15\u2009bp downstream, leading to in frame deletion of five amino acid residues (p.Phe611_Gly615del). The predicted in frame deletion clusters with all the mutations previously identified in XCVD and falls within the N\u2010terminus rod 1 domain of filamin A. Our findings expand the male\u2010specific phenotype of <jats:italic>FLNA<\/jats:italic> mutations that now includes classical\u2010like EDS with lethal cardiac valvular dystrophy, and offer further insights for the genotype\u2013phenotype correlations within this spectrum. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38004","type":"journal-article","created":{"date-parts":[[2016,10,14]],"date-time":"2016-10-14T06:34:37Z","timestamp":1476426877000},"page":"169-176","source":"Crossref","is-referenced-by-count":17,"title":["Ehlers\u2013Danlos syndrome with lethal cardiac valvular dystrophy in males carrying a novel splice mutation in <i>FLNA<\/i>"],"prefix":"10.1002","volume":"173","author":[{"given":"Marco","family":"Ritelli","sequence":"first","affiliation":[{"name":"Division of Biology and Genetics Department of Molecular and Translational Medicine School of Medicine University of Brescia Brescia 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