{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T21:13:48Z","timestamp":1766870028211,"version":"3.41.2"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T00:00:00Z","timestamp":1565222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Male <jats:italic>EBP<\/jats:italic> disorder with neurologic defects (MEND) syndrome is an X\u2010linked disease caused by hypomorphic\u00a0mutations in the <jats:italic>EBP<\/jats:italic> (emopamil\u2010binding protein)\u00a0gene. Modifier genes may explain the clinical variability among individuals who share a primary mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied four males (Patient 1 to Patient 4) exhibiting a descending degree of phenotypic severity from a family with MEND syndrome. To identify candidate modifier genes that explain the phenotypic variability, variants of homeostasis cholesterol genes identified by whole\u2010exome sequencing (WES) were ranked according to the predicted magnitude of their effect through an in\u2010house scoring system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010seven from 105 missense variants found in 45 genes of the four exomes were considered significant (\u22125 to \u22129 scores). We found a direct genotype\u2013phenotype association based on the differential accumulation of potentially functional gene variants among males. Patient 1 exhibited 17 variants, both Patients 2 and 3 exhibited nine variants, and Patient 4 exhibited only five variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conclude that <jats:italic>APOA5<\/jats:italic> (rs3135506)<jats:italic>, ABCA1<\/jats:italic> (rs9282541), and <jats:italic>APOB<\/jats:italic> (rs679899 and rs12714225) are the most relevant candidate modifier genes in this family. Relative accumulation of the deficiencies associated with variants of these genes along with other lesser deficiencies in other genes appears to explain the variable expressivity in MEND syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.931","type":"journal-article","created":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T05:09:28Z","timestamp":1565327368000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Phenotypic severity in a family with MEND syndrome is directly associated with the accumulation of potentially functional variants of cholesterol homeostasis genes"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-6676","authenticated-orcid":false,"given":"Mar\u00eda Carmen","family":"Barboza\u2010Cerda","sequence":"first","affiliation":[{"name":"Facultad de Medicina y Hospital Universitario \u201cDr. Jos\u00e9 E. Gonz\u00e1lez\u201d Servicio de Anatom\u00eda Patol\u00f3gica y Citopatolog\u00eda, Universidad Aut\u00f3noma de Nuevo Le\u00f3n Monterrey Nuevo Le\u00f3n Mexico"},{"name":"Facultad de Medicina y Hospital Universitario \u201cDr. Jos\u00e9 E. Gonz\u00e1lez\u201d, Departamento de Bioqu\u00edmica y Medicina Molecular Universidad Aut\u00f3noma de Nuevo Le\u00f3n Monterrey Nuevo Le\u00f3n Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0979-3900","authenticated-orcid":false,"given":"Oralia","family":"Barboza\u2010Quintana","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Hospital Universitario \u201cDr. Jos\u00e9 E. Gonz\u00e1lez\u201d Servicio de Anatom\u00eda Patol\u00f3gica y Citopatolog\u00eda, Universidad Aut\u00f3noma de Nuevo Le\u00f3n Monterrey Nuevo Le\u00f3n Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo","family":"Mart\u00ednez\u2010Aldape","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Hospital Universitario \u201cDr. Jos\u00e9 E. Gonz\u00e1lez\u201d Servicio de Anatom\u00eda Patol\u00f3gica y Citopatolog\u00eda, Universidad Aut\u00f3noma de Nuevo Le\u00f3n Monterrey Nuevo Le\u00f3n Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2955-1212","authenticated-orcid":false,"given":"Raquel","family":"Garza\u2010Guajardo","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Hospital Universitario \u201cDr. Jos\u00e9 E. 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