{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T17:23:16Z","timestamp":1778088196820,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,11,11]],"date-time":"2016-11-11T00:00:00Z","timestamp":1478822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Pyrroline\u20105\u2010carboxylate reductase 2, encoded by <jats:italic>PYCR2<\/jats:italic>, is one of the three homologous enzymes that catalyze the last step of proline synthesis. Homozygous variants in <jats:italic>PYCR2<\/jats:italic> have been reported in patients from multiple consanguineous families with hypomyelinating leukodystrophy 10 (HLD10) (MIM: 616420). Here, we report five additional patients from three families with homozygous nonsense or missense variants in <jats:italic>PYCR2<\/jats:italic>, identified through clinical exome sequencing. All patients presented with postnatally acquired microcephaly, moderate to profound global developmental delay, and failure to thrive. Brain MRI in these patients showed thin corpus callosum, delayed myelination, and generalized white\u2010matter volume loss. Additional phenotypes that were less consistent among patients included seizures or seizure\u2010like movements, spasticity and ataxic gait, recurrent vomiting, cortical blindness, dysmorphic features, joint contractures, and irritability. Exome sequencing identified homozygous variants in <jats:italic>PYCR2<\/jats:italic> in the proband from each family: c.28C&gt;T (p.(Glu10Ter)), c.796C&gt;T (p.(Arg266Ter)), and c.577G&gt;A (p.(Val193Met)). Subsequent targeted analyses demonstrated co\u2010segregation of the disease with the variant in the family. Despite the metabolic role of PYCR2, routine serum metabolic test in these patients were normal. To further understand the disease etiology and functions of PYCR2, small molecule metabolomics profiling was performed in plasma from three severely affected patients. No significant changes were identified in proline biosynthesis pathway or related metabolites. Studying the clinical features and the metabolic profiles of the PYCR2\u2010deficient patients provides a more comprehensive picture for this newly identified disorder and facilitates further research on the gene function and disease etiology. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38049","type":"journal-article","created":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T14:39:29Z","timestamp":1479134369000},"page":"460-470","source":"Crossref","is-referenced-by-count":21,"title":["Homozygous variants in <i>pyrroline\u20105\u2010carboxylate reductase 2<\/i> (<i>PYCR2<\/i>) in patients with progressive microcephaly and hypomyelinating leukodystrophy"],"prefix":"10.1002","volume":"173","author":[{"given":"Linyan","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"},{"name":"Baylor Genetics Houston 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