Three patients with Schaaf–Yang syndrome exhibiting arthrogryposis and endocrinological abnormalities |
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| Authors: | Takuji Enya Nobuhiko Okamoto Yoshinori Iba Tomoki Miyazawa Mitsuru Okada Shinobu Ida Takuya Naruto Issei Imoto Atsushi Fujita Noriko Miyake Naomichi Matsumoto Keisuke Sugimoto Tsukasa Takemura |
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| Affiliation: | 1. Department of Pediatrics, Kindai University Faculty of Medicine, Osaka, Japan;2. Department of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan;3. Department of Molecular Medicine, Osaka Women's and Children's Hospital, Osaka, Japan;4. Department of Pediatric Gastroenterology, Nutrition and Endocrinology, Osaka Women's and Children's Hospital, Osaka, Japan;5. Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan;6. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan |
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| Abstract: | ![]()
MAGEL2 is the paternally expressed gene within Prader–Willi syndrome critical region at 15q11.2. We encountered three individuals in whom truncating mutations of MAGEL2 were identified. Patients 1 and 2, siblings born to healthy, non‐consanguineous Japanese parents, showed generalized hypotonia, lethargy, severe respiratory difficulty, poor feeding, and multiple anomalies including arthrogryposis soon after birth. We carried out whole‐exome sequencing, which detected a MAGEL2 mutation (c.1912C>T, p.Gln638*, heterozygous). The patients’ father was heterozygous for the mutation. Patient 3 was a female infant, showed respiratory difficulty reflecting pulmonary hypoplasia, generalized hypotonia, feeding difficulty and multiple anomalies soon after birth. Targeted next‐generation sequencing detected a novel heterozygous mutation in MAGEL2 (c.3131C>A, p.Ser1044*). This mutation was not found in the parents. MAGEL2 mutations, first reported to be the cause of the Prader–Willi like syndrome with autism by Schaaf et al. (2013) Nature Genetics, 45: 1405–1408 show the wide range of phenotypic spectrum from lethal arthrogryposis multiplex congenital to autism spectrum disorder (ASD) and mild intellectual disability (ID). Our results indicate that MAGEL2 mutations cause multiple congenital anomalies and intellectual disability accompanied by arthrogryposis multiplex congenita and various endocrinologic abnormalities, supporting that the view that clinical phenotypes of MAGEL2 mutations are variable. |
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| Keywords: | arthrogryposis multiplex congenita endocrinologic abnormalities MAGEL2 Prader– Willi syndrome Schaaf– Yang syndrome |
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