{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:19:27Z","timestamp":1767626367855,"version":"3.41.2"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Filamin A, encoded by the X\u2010linked gene <jats:italic>FLNA<\/jats:italic>, links the cell membrane with the cytoskeleton and acts as a regulator of the actin cytoskeleton. Mutations in <jats:italic>FLNA<\/jats:italic> cause a large spectrum of congenital malformations during embryonic development, including Melnick\u2013Needles syndrome (MNS). However, reports of MNS, especially in males, are rare, and the pathogenesis molecular mechanisms are not well understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We found a family with two consecutive miscarriages of similar fetuses with multiple malformations. DNA was extracted from peripheral blood and tissues, and whole exome sequencing was performed for genetic analysis. Then, we created a C57BL\/6 mouse with a point mutation by CRISPR\/Cas\u2010mediated genome engineering. The migration of primary abdominal muscle cell was detected by wound healing assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The first fetus showed congenital hygroma colli and omphalocele identified by ultrasound at 12 wks; the second fetus showed hygroma colli and thoraco abdominoschisis at 12 wks, with a new hemizygous mutation c.4420G&gt;A in exon 26 of the <jats:italic>FLNA<\/jats:italic> gene, which is predicted to cause an amino acid substitution (p.Asp1474Asn). The mother and grandmother were both present in the c.4420G&gt;A heterozygous state, and the mother's healthy brother had wild\u2010type <jats:italic>FLNA<\/jats:italic>. These <jats:italic>FLNA<\/jats:italic>\u2010mutated mice exhibited a broader central gap between the rectus abdominis than the wild type (WT), similar to the midline structure dysplasia of the abdominal wall in the two fetuses. Wound healing assays showed the attenuated migration capacity of abdominal muscle cells in mice with mutated <jats:italic>FLNA<\/jats:italic>. Finally, we summarized the cases of MNS with <jats:italic>FLNA<\/jats:italic> mutation from the accessible published literature thus far.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our research revealed a mutation site of the <jats:italic>FLNA<\/jats:italic> for MNS and explored the mechanism of midline structure dysplasia in the abdominal wall of male patients, which could provide more evidence for the clinical diagnosis and genetic counseling of families with these disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2145","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T08:44:41Z","timestamp":1675413881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mutation of <i>FLNA<\/i> attenuating the migration of abdominal muscles contributed to Melnick\u2013Needles syndrome (<scp>MNS<\/scp>) in a family with recurrent miscarriage"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6998-6141","authenticated-orcid":false,"given":"Xin","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology The Third Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zailin","family":"Yang","sequence":"additional","affiliation":[{"name":"Chongqing University Cancer Hospital  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Yubei District Chinese Medicine Hospital  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Third Affiliated Hospital of Chongqing Medical University  Chongqing 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