{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:31:32Z","timestamp":1790641892270,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Biallelic <jats:italic>RNPC3<\/jats:italic> variants have been reported in a few patients with growth hormone deficiency, either in isolation or in association with central hypothyroidism, congenital cataract, neuropathy, developmental delay\/intellectual disability, hypogonadism, and pituitary hypoplasia. To describe a new patient with syndromic congenital hypopituitarism and diffuse brain atrophy due to <jats:italic>RNPC3<\/jats:italic> mutations and to compare her clinical and molecular characteristics and pituitary functions with previously published patients. A 20\u2010year\u2010old female presented with severe growth, neuromotor, and developmental delay. Her weight, height, and head circumference were 5135 gr (\u221225.81 SDS), 68\u2009cm (\u221216.17 SDS), and 34\u2009cm (\u221217.03 SDS), respectively. She was prepubertal, and had dysmorphic facies, contractures, and spasticity in the extremities, and severe truncal hypotonia. There were no radiological signs of a skeletal dysplasia. The bone age was extremely delayed at 2\u2009years. Investigation of pituitary function revealed growth hormone, prolactin, and thyroid\u2010stimulating hormone deficiencies. Whole\u2010exome sequencing revealed a novel homozygous missense (c.1328A\u2009&gt;\u2009G; Y443C) variant in <jats:italic>RNPC3<\/jats:italic>. Cranial MRI revealed a hypoplastic anterior pituitary with diffuse cerebral and cerebellar atrophy. The Y443C variant in <jats:italic>RNPC3<\/jats:italic> associated with syndromic congenital hypopituitarism and abnormal brain development. This report extends the <jats:italic>RNPC3<\/jats:italic>\u2010related hypopituitarism phenotype with a severe neurodegenerative presentation.<\/jats:p>","DOI":"10.1002\/ajmg.a.62888","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T16:07:52Z","timestamp":1657123672000},"page":"2701-2706","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A homozygous <scp>Y443C<\/scp> variant in the <scp><i>RNPC3<\/i><\/scp> is associated with severe syndromic congenital hypopituitarism and diffuse brain atrophy"],"prefix":"10.1002","volume":"188","author":[{"given":"Di\u011fdem","family":"Bezen","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Pediatric Endocrinology University of Health Sciences, Prof. Dr. Cemil Ta\u015f\u00e7\u0131o\u011flu City Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orkide","family":"Kutlu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Health Sciences, Prof. Dr. Cemil Ta\u015f\u00e7\u0131o\u011flu City Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Mouilleron","sequence":"additional","affiliation":[{"name":"Structural Biology Science Technology Platforms The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Rizzoti","sequence":"additional","affiliation":[{"name":"Stem Cell Biology and Developmental Genetics Lab The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-5809","authenticated-orcid":false,"given":"Mehul","family":"Dattani","sequence":"additional","affiliation":[{"name":"Department and Genetics and Genomic Medicine Research and Teaching UCL GOS Institute of Child Health  London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2658-6866","authenticated-orcid":false,"given":"Tulay","family":"Guran","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, School of Medicine Marmara University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6zde","family":"Ye\u015fil","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Pediatric Genetics, Istanbul Medical Faculty Istanbul University  Istanbul 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