{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T04:38:41Z","timestamp":1789274321189,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,7,20]],"date-time":"2015-07-20T00:00:00Z","timestamp":1437350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>Congenital generalized lipodystrophy (<jats:styled-content style=\"fixed-case\">CGL<\/jats:styled-content>) is an autosomal recessive disorder with two major subtypes. Variants in <jats:italic><jats:styled-content style=\"fixed-case\">AGPAT2<\/jats:styled-content><\/jats:italic> result in <jats:styled-content style=\"fixed-case\">CGL<\/jats:styled-content> type 1 with milder manifestations, whereas <jats:italic><jats:styled-content style=\"fixed-case\">BSCL2<\/jats:styled-content><\/jats:italic> variants cause <jats:styled-content style=\"fixed-case\">CGL<\/jats:styled-content> type 2 with more severe features. Muscle hypertrophy caused by lack of adipose tissue is present early in life in <jats:styled-content style=\"fixed-case\">CGL<\/jats:styled-content> patients. Our aim was to investigate 10 <jats:styled-content style=\"fixed-case\">CGL<\/jats:styled-content> patients from 7 different countries and report genotype\u2013phenotype relationships. Genetic analysis identified disease\u2010causing variants in <jats:italic><jats:styled-content style=\"fixed-case\">AGPAT2<\/jats:styled-content><\/jats:italic> (five patients) and in <jats:italic><jats:styled-content style=\"fixed-case\">BSCL2<\/jats:styled-content><\/jats:italic> (five patients), including three novel variants; c.<jats:styled-content style=\"fixed-case\">134C<\/jats:styled-content>&gt;A (p.Ser45*), c.<jats:styled-content style=\"fixed-case\">216C<\/jats:styled-content>&gt;G (p.Tyr72*) in <jats:italic><jats:styled-content style=\"fixed-case\">AGPAT2<\/jats:styled-content><\/jats:italic> and c.<jats:styled-content style=\"fixed-case\">458C<\/jats:styled-content>&gt;A (p.Ser153*) in <jats:italic><jats:styled-content style=\"fixed-case\">BSCL2<\/jats:styled-content><\/jats:italic>. We also report possible novel clinical features such as anemia, breast enlargement, steatorrhea, intraventricular hemorrhage and nephrolithiasis in <jats:styled-content style=\"fixed-case\">CGL<\/jats:styled-content> patients. Generalized lipodystrophy and muscular hypertrophy were the only features in all of our patients. Hepatomegaly was the second common feature. Some manifestations were exclusively noticed in our <jats:styled-content style=\"fixed-case\">CGL2<\/jats:styled-content> patients; hypertrichosis, high\u2010pitched voice and umbilical hernia. Bone cysts and history of seizures were noticed only in <jats:styled-content style=\"fixed-case\">CGL1<\/jats:styled-content> patients. The findings of this study expand our knowledge of genotype\u2013phenotype correlations in <jats:styled-content style=\"fixed-case\">CGL<\/jats:styled-content> patients. These results have important clinical applications in diagnosis and management of the <jats:styled-content style=\"fixed-case\">CGL<\/jats:styled-content> patients as well as in genetic counseling in families at\u2010risk.<\/jats:p>","DOI":"10.1111\/cge.12623","type":"journal-article","created":{"date-parts":[[2015,6,15]],"date-time":"2015-06-15T08:25:34Z","timestamp":1434356734000},"page":"434-441","source":"Crossref","is-referenced-by-count":23,"title":["Congenital generalized lipodystrophy: identification of novel variants and expansion of clinical spectrum"],"prefix":"10.1111","volume":"89","author":[{"given":"A.","family":"Haghighi","sequence":"first","affiliation":[{"name":"Department of Genetics Harvard Medical School  Boston MA USA"},{"name":"Department of Medicine and the Howard Hughes Medical Institute Brigham and Women's Hospital  Boston MA USA"},{"name":"Wellcome Trust Centre for Human Genetics University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Kavehmanesh","sequence":"additional","affiliation":[{"name":"Research Center for Gastroenterology and Liver Diseases Baqiyatallah University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Haghighi","sequence":"additional","affiliation":[{"name":"Toronto General Hospital University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Salehzadeh","sequence":"additional","affiliation":[{"name":"Pediatric Department, Bouali Hospital Ardabil University of Medical Sciences  Ardabil Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Santos\u2010Simarro","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras ISCIII  Madrid Spain"},{"name":"Clinical Genetics Unit, INGEMM, IdiPAZ Hospital Universitario La Paz, UAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Van Maldergem","sequence":"additional","affiliation":[{"name":"Centre de g\u00e9n\u00e9tique humaine Universit\u00e9 de FRanche\u2010Comt\u00e9  Besan\u00e7on France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Cimbalistiene","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics Vilnius University  Vilnius Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Children's Hospital at Westmead  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Chopra","sequence":"additional","affiliation":[{"name":"Department of Medical Genomics Royal Prince Alfred Hospital, Camperdown  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Al\u2010Sinani","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Department of Child Health Sultan Qaboos University Hospital  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Dastmalchian","sequence":"additional","affiliation":[{"name":"Case Medical Center Case Western Reserve University  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.C.","family":"de Silva","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine University of Kelaniya  Ragama Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Bakhti","sequence":"additional","affiliation":[{"name":"Pathology Department Takht\u2010e Jamshid Hospital  Karaj Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Garg","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases, Department of Internal Medicine and the Center for Human Nutrition UT Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Hilbert","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Genetics  Gosselies Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-14-2-193"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1959.tb17558.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1996.tb14262.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra025261"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(99)00414-3"},{"key":"e_1_2_6_7_1","volume-title":"Berardinelli\u2010Seip congenital lipodystrophy. 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