<i>PTPN11</i> and <i>FLNA</i> variants in a boy with ambiguous genitalia, short stature, and non-specific dysmorphic features
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- Muranishi Yuki
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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- Itonaga Tomoyo
- Department of Pediatrics, Oita University Faculty of Medicine, Yufu, Japan
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- Ihara Kenji
- Department of Pediatrics, Oita University Faculty of Medicine, Yufu, Japan
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- Katoh-Fukui Yuko
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan
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- Tamaoka Satoshi
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan
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- Hattori Atsushi
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan
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- Kon Masafumi
- Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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- Shinohara Nobuo
- Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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- Fukami Maki
- Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan
抄録
<p>Noonan syndrome is a congenital disorder characterized by distinctive facial appearance, congenital heart defects, short stature, and skeletal dysplasia. Although boys with Noonan syndrome frequently exhibit cryptorchidism, a mild form of 46,XY disorders of sex development (DSD), they barely manifest more severe genital abnormalities. Here, we report a boy with ambiguous genitalia, short stature, and non-specific dysmorphic features. He had no cardiac abnormalities or skeletal dysplasia. His score in the Noonan syndrome diagnostic criteria (36 of 157 points, 23%) was lower than the cutoff for diagnosis (50%). Whole-exome sequencing identified a de novo heterozygous variant (c.922A>G: p.Asn308Asp) in PTPN11 and a maternally inherited hemizygous variant (c.1439C>T: p.Pro480Leu) in FLNA. The PTPN11 variant was a known causative mutation for Noonan syndrome. FLNA is a causative gene for neurodevelopmental and skeletal abnormalities and has also been implicated in 46,XY DSD. The p.Pro480Leu variant of FLNA was assessed as deleterious by in silico analyses. These results provide evidence that whole-exome sequencing is a powerful tool for diagnosing patients with atypical disease manifestations. Furthermore, our data suggest a possible role of digenic mutations as phenotypic modifiers of Noonan syndrome.</p>
収録刊行物
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- Clinical Pediatric Endocrinology
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Clinical Pediatric Endocrinology advpub (0), 2024
日本小児内分泌学会
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詳細情報 詳細情報について
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- CRID
- 1390300014546296832
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- ISSN
- 13477358
- 09185739
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- 本文言語コード
- en
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- データソース種別
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- JaLC
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- 抄録ライセンスフラグ
- 使用不可