{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:18Z","timestamp":1772160078229,"version":"3.50.1"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Glutathione synthetase deficiency is a rare inborn metabolic disease usually caused by biallelic variants in\n                    <jats:italic>GSS<\/jats:italic>\n                    . Clinical severity varies from isolated hemolytic anemia, sometimes associated with chronic metabolic acidosis and 5\u2010oxoprolinuria, to severe neurological phenotypes with neonatal lethality. Here we report on two fetal siblings from two pregnancies with glutathione synthetase deficiency exhibiting similar multiple congenital anomalies associating phocomelia, cleft palate, intra\u2010uterine growth retardation, genito\u2010urinary malformations, and congenital heart defect. Genome sequencing showed that both fetuses were compound heterozygous for two\n                    <jats:italic>GSS<\/jats:italic>\n                    variants: the previously reported pathogenic missense substitution NM_000178.4 c.800G&gt;A p.(Arg267Gln), and a 2.4\u2009kb intragenic deletion NC_000020.11:g.34944530_34946833del. RNA\u2010seq on brain tissue revealed the out\u2010of\u2010frame deletion of the exon 3 and an almost monoallelic expression of the missense variant (88%), suggesting degradation of the deletion\u2010harboring allele by nonsense\u2010mediated mRNA decay. 5\u2010oxoproline (pyroglutamic acid) levels in amniotic fluid were elevated, suggesting an alteration of the gamma\u2010glutamyl cycle, and corroborating the pathogenicity of the two\n                    <jats:italic>GSS<\/jats:italic>\n                    variants. Only one case of glutathione synthetase deficiency with limb malformations has previously been reported, in a newborn homozygous for the c.800G&gt;A variant. Thus, our data allow us to discuss a potential phenotypic extension of glutathione synthetase deficiency, with a possible involvement of the c.800G&gt;A variant.\n                  <\/jats:p>","DOI":"10.1111\/cge.14613","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T08:43:39Z","timestamp":1725266619000},"page":"776-781","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiple congenital anomalies in two fetuses with glutathione\u2010synthetase deficit (\n                    <i>GSS<\/i>\n                    )"],"prefix":"10.1111","volume":"106","author":[{"given":"Jeanne","family":"Jury","sequence":"first","affiliation":[{"name":"Service de G\u00e9n\u00e9tique m\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5389-8585","authenticated-orcid":false,"given":"Jean\u2010Fran\u00e7ois","family":"Benoist","sequence":"additional","affiliation":[{"name":"Laboratoire de Biochimie M\u00e9tabolique H\u00f4pital Necker\u2010Enfants\u2010Malades, APHP  Paris France"},{"name":"CEA, INRAE, DMTS, SPI, MetaboHUB\u2010IDF Universit\u00e9 Paris\u2010Saclay  Gif\u2010sur\u2010Yvette France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeleine","family":"Joubert","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de F\u0153topathologie et G\u00e9n\u00e9tique CHU de Nantes  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chlo\u00e9","family":"Quelin","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique, CLAD Ouest CHU Rennes, H\u00f4pital Sud  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Besnard","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique m\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"},{"name":"l'institut du thorax Nantes Universit\u00e9, CHU de Nantes, CNRS, INSERM  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sol\u00e8ne","family":"Conrad","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique m\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudine","family":"Le Vaillant","sequence":"additional","affiliation":[{"name":"Service de Gyn\u00e9cologie et Obst\u00e9trique CHU Nantes  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane","family":"B\u00e9zieau","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique m\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"},{"name":"l'institut du thorax Nantes Universit\u00e9, CHU de Nantes, CNRS, INSERM  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique m\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"},{"name":"l'institut du thorax Nantes Universit\u00e9, CHU de Nantes, CNRS, INSERM  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Atti\u00e9\u2010Bitach","sequence":"additional","affiliation":[{"name":"Imagine Institute, INSERM UMR1163  Paris France"},{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies Rares H\u00f4pital Necker\u2010Enfants Malades, Assistance Publique\u2010H\u00f4pitaux de Paris, Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Paris Cit\u00e9  Paris France"},{"name":"Laboratoire SeqOIA (PFMG 2025)  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Cogn\u00e9","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique m\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"},{"name":"l'institut du thorax Nantes Universit\u00e9, CHU de Nantes, CNRS, INSERM  Nantes France"},{"name":"Laboratoire SeqOIA (PFMG 2025)  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Vincent","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique m\u00e9dicale Nantes Universit\u00e9, CHU de Nantes  Nantes France"},{"name":"l'institut du thorax Nantes Universit\u00e9, CHU de Nantes, CNRS, INSERM  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-361"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.07.056"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/15513815.2019.1627627"},{"issue":"425","key":"e_1_2_7_5_1","first-page":"425","article-title":"\u8c37\u80f1\u7518\u80bd\u5408\u6210\u9176\u7f3a\u4e4f\u75c7\u5e76\u6587\u732e\u590d\u4e60","volume":"17","author":"Qiuping 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