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A 30 Mainland Chinese cohort of patients with Phelan-McDermid syndrome: genotype-phenotype correlation and the role of SHANK3 haploinsufficiency in the important phenotypes
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  • Na Xu,
  • Hui Lv,
  • Tingting Yang,
  • Xiujuan Du,
  • Yu Sun,
  • Bing Xiao,
  • Yanjie Fan,
  • Xiaomei Luo,
  • Yongkun Zhan,
  • Lili Wang,
  • Fei Li,
  • Yongguo Yu
Na Xu
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research
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Hui Lv
Department of Developmental and Behavioral Pediatrics, Department of Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research & MOE-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
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Tingting Yang
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research
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Xiujuan Du
Department of Developmental and Behavioral Pediatrics, Department of Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research & MOE-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
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Yu Sun
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research
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Bing Xiao
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research
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Yanjie Fan
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research
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Xiaomei Luo
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research
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Yongkun Zhan
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research
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Lili Wang
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research
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Fei Li
Department of Developmental and Behavioral Pediatrics, Department of Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research & MOE-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
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Yongguo Yu
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition
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Abstract

This is the first study describing a cohort of Mainland China patients broaden the clinical and molecular spectrum of Phelan-McDermid syndrome (PMS) or 22q13 deletion syndrome. A total of 30 Mainland China patients were clinically and genetically evaluated. We discover that nineteen patients with 22q13.3 deletions, one patient with terminal deletions and duplications, one patient with duplications, and nine patients with SHANK3 mutations were included. Six novel heterozygous variants, c.3838_3839insGG, c.3088delC, c.3526G>T, c.3372dupC, c.3120delC and c.3942delC, were firstly reported. Besides, we demonstrated speech delay, DD/ID, ASD, hypotonia and hyperactivity were prominent clinical features. Since most reported cases used to genotype-phenotype analyses are caused by 22q13 deletions usually encompassing many genes including SHANK3, we performed genotype-phenotype analysis, and found hypotonia was 100% of cases with loss of SHANK3 alone and there was no significant difference between loss of SHANK3 alone and deletions encompass more than SHANK3 gene regarding hypotonia, DD/ID, ASD, increased pain tolerance, gait abnormalities, impulsiveness, repetitive behaviors, regression and nonstop crying which are high frequency in loss of SHANK3 alone group. This analysis improves the understanding that SHANK3 haploinsufficiency is a major contributor to the neurological phenotypes of PMS and also responsible for other important phenotypes such as hypotonia.