1. A homozygous <scp>Y443C</scp> variant in the <scp> RNPC3 </scp> is associated with severe syndromic congenital hypopituitarism and diffuse brain atrophy
- Author
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Diğdem Bezen, Orkide Kutlu, Stephane Mouilleron, Karine Rizzoti, Mehul Dattani, Tulay Guran, Gözde Yeşil, Bezen D., Kutlu O., Mouilleron S., Rizzoti K., Dattani M., Güran T., Yesil G., and Bezen D., Kutlu O., Mouilleron S., Rizzoti K., Dattani M., GÜRAN T., Yesil G.
- Subjects
Internal Diseases ,GENETİK VE KALITIM ,Endocrinology, Diabetes and Metabolism ,Endocrinology and Metabolic Diseases ,Sağlık Bilimleri ,Pediatrics ,İç Hastalıkları ,Clinical Medicine (MED) ,Endocrinology ,DEVELOPMENTAL DISORDER ,Klinik Tıp (MED) ,Pediatri, Perinatoloji ve Çocuk Sağlığı ,GENETICS & HEREDITY ,MUTATION ,Genetics (clinical) ,Klinik Tıp ,Moleküler Biyoloji ,MINOR SPLICEOSOME ,Temel Bilimler ,RNU4ATAC ,neurodegeneration ,Life Sciences ,Tıp ,MOLECULAR BIOLOGY & GENETICS ,ENDOKRİNOLOJİ VE METABOLİZMA ,Medicine ,PEDİATRİ ,Natural Sciences ,Medical Genetics ,Endokrin ve Otonom Sistemler ,ENDOCRINOLOGY & METABOLISM ,Life Sciences (LIFE) ,Molecular Biology and Genetics ,Endokrinoloji ,Çocuk Sağlığı ve Hastalıkları ,Child Health and Diseases ,syndromic congenital hypopituitarism ,Tıbbi Genetik ,Yaşam Bilimleri ,Health Sciences ,Genetics ,Genetik ,Molecular Biology ,Moleküler Biyoloji ve Genetik ,Internal Medicine Sciences ,Endocrine and Autonomic Systems ,Dahili Tıp Bilimleri ,CLINICAL MEDICINE ,RNPC3 ,COMPONENT ,Pediatri ,Yaşam Bilimleri (LIFE) ,Pediatrics, Perinatology and Child Health ,Endokrinoloji ve Metabolizma Hastalıkları ,Genetik (klinik) ,neuropathy ,Endokrinoloji, Diyabet ve Metabolizma ,brain atrophy - Abstract
Biallelic RNPC3 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 RNPC3 mutations and to compare her clinical and molecular characteristics and pituitary functions with previously published patients. A 20-year-old female presented with severe growth, neuromotor, and developmental delay. Her weight, height, and head circumference were 5135 gr (-25.81 SDS), 68 cm (-16.17 SDS), and 34 cm (-17.03 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 years. Investigation of pituitary function revealed growth hormone, prolactin, and thyroid-stimulating hormone deficiencies. Whole-exome sequencing revealed a novel homozygous missense (c.1328A > G; Y443C) variant in RNPC3. Cranial MRI revealed a hypoplastic anterior pituitary with diffuse cerebral and cerebellar atrophy. The Y443C variant in RNPC3 associated with syndromic congenital hypopituitarism and abnormal brain development. This report extends the RNPC3-related hypopituitarism phenotype with a severe neurodegenerative presentation.
- Published
- 2022