{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:44:27Z","timestamp":1791287067056,"version":"4.1.0"},"reference-count":50,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> The gene encoding fatty acid CoA ligase 4 (<jats:italic>FACL4<\/jats:italic>) is mutated in families with non-specific X linked mental retardation (MRX) and is responsible for cognitive impairment in the contiguous gene syndrome ATS-MR (Alport syndrome and mental retardation), mapped to Xq22.3. This finding makes this gene a good candidate for other mental retardation disorders mapping in this region.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> We have screened the <jats:italic>FACL4<\/jats:italic> gene in eight families, two MRX and six syndromic X linked mental retardation (MRXS), mapping in a large interval encompassing Xq22.3.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> We have found a missense mutation in MRX68. The mutation (c.1001C&gt;T in the brain isoform) cosegregates with the disease and changes a highly conserved proline into a leucine (p.P375L) in the first luciferase domain, which markedly reduces the enzymatic activity. Furthermore, all heterozygous females showed completely skewed X inactivation in blood leucocytes, as happens in all reported females with other <jats:italic>FACL4<\/jats:italic> point mutations or deletions.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusions:<\/jats:bold> Since the <jats:italic>FACL4<\/jats:italic> gene is highly expressed in brain, where it encodes a brain specific isoform, and is located in hippocampal and cerebellar neurones, a role for this gene in cognitive processes can be expected. Here we report the third MRX family with a <jats:italic>FACL4<\/jats:italic> mutation and describe the development of a rapid enzymatic assay on peripheral blood that we propose as a sensitive, robust, and efficient diagnostic tool in mentally retarded males.<\/jats:p>","DOI":"10.1136\/jmg.40.1.11","type":"journal-article","created":{"date-parts":[[2003,1,13]],"date-time":"2003-01-13T20:03:33Z","timestamp":1042488213000},"page":"11-17","source":"Crossref","is-referenced-by-count":39,"title":["A third MRX family (MRX68) is the result of mutation in the long chain fatty acid-CoA ligase 4 (<i>FACL4<\/i>) gene: proposal of a rapid enzymatic assay for screening mentally retarded patients"],"prefix":"10.1136","volume":"40","author":[{"given":"I","family":"Longo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S G M","family":"Frints","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J-P","family":"Fryns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Meloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Pescucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Ariani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Borghgraef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Raynaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Marynen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Renieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Froyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2003,1,1]]},"reference":[{"key":"2025100521074718000_40.1.11.1","unstructured":"American Psychiatric Association. 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