The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy
Abstract Background Wolf-Hirschhorn syndrome is a well-characterized genomic disorder caused by 4p16.3 deletions. Wolf-Hirschhorn syndrome patients exhibit characteristic facial dysmorphism, growth retardation, developmental delay, intellectual disability and seizure disorders. Recently, NSD2 gene l...
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doaj-d4c661cb04684f588cc683af2eed8a342021-04-02T16:20:52ZengBMCBMC Medical Genomics1755-87942020-12-011311810.1186/s12920-020-00831-9The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapyXuyun Hu0Di Wu1Yuchuan Li2Liya Wei3Xiaoqiao Li4Miao Qin5Hongdou Li6Mengting Li7Shaoke Chen8Chunxiu Gong9Yiping Shen10Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthDepartment of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthDepartment of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthDepartment of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthDepartment of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthDepartment of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthObstetrics Gynecology Hospital, The Institute of Reproduction and Developmental Biology, Fudan UniversityGenetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous RegionThe second affiliated hospital of Guangxi Medical UniversityBeijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s HealthGenetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous RegionAbstract Background Wolf-Hirschhorn syndrome is a well-characterized genomic disorder caused by 4p16.3 deletions. Wolf-Hirschhorn syndrome patients exhibit characteristic facial dysmorphism, growth retardation, developmental delay, intellectual disability and seizure disorders. Recently, NSD2 gene located within the 165 kb Wolf-Hirschhorn syndrome critical region was identified as the key causal gene responsible for most if not all phenotypes of Wolf-Hirschhorn syndrome. So far, eight NSD2 loss of function variants have been reported in patients from different parts of the world, all were de novo variants. Methods In our study, we performed whole exome sequencing for two patients from one family. We also reviewed more NSD2 mutation cases in pervious literature. Results A novel loss of function NSD2 variant, c.1577dupG (p.Asn527Lysfs*14), was identified in a Chinese family in the proband and her father both affected with intellectual disability. After reviewing more NSD2 mutation cases in pervious literature, we found none of them had facial features that can be recognized as Wolf-Hirschhorn syndrome. In addition, we have given our proband growth hormone and followed up with this family for 7.5 years. Conclusions Here we reported the first familial NSD2 variant and the long-term effect of growth hormone therapy for patients. Our results suggested NSD2 mutation might cause a distinct intellectual disability and short stature syndrome.https://doi.org/10.1186/s12920-020-00831-9Wolf-Hirschhorn syndromeNSD2 geneGrowth hormone therapyFacial dysmorphismIntellectual disability |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuyun Hu Di Wu Yuchuan Li Liya Wei Xiaoqiao Li Miao Qin Hongdou Li Mengting Li Shaoke Chen Chunxiu Gong Yiping Shen |
spellingShingle |
Xuyun Hu Di Wu Yuchuan Li Liya Wei Xiaoqiao Li Miao Qin Hongdou Li Mengting Li Shaoke Chen Chunxiu Gong Yiping Shen The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy BMC Medical Genomics Wolf-Hirschhorn syndrome NSD2 gene Growth hormone therapy Facial dysmorphism Intellectual disability |
author_facet |
Xuyun Hu Di Wu Yuchuan Li Liya Wei Xiaoqiao Li Miao Qin Hongdou Li Mengting Li Shaoke Chen Chunxiu Gong Yiping Shen |
author_sort |
Xuyun Hu |
title |
The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy |
title_short |
The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy |
title_full |
The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy |
title_fullStr |
The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy |
title_full_unstemmed |
The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy |
title_sort |
first familial nsd2 cases with a novel variant in a chinese father and daughter with atypical whs facial features and a 7.5-year follow-up of growth hormone therapy |
publisher |
BMC |
series |
BMC Medical Genomics |
issn |
1755-8794 |
publishDate |
2020-12-01 |
description |
Abstract Background Wolf-Hirschhorn syndrome is a well-characterized genomic disorder caused by 4p16.3 deletions. Wolf-Hirschhorn syndrome patients exhibit characteristic facial dysmorphism, growth retardation, developmental delay, intellectual disability and seizure disorders. Recently, NSD2 gene located within the 165 kb Wolf-Hirschhorn syndrome critical region was identified as the key causal gene responsible for most if not all phenotypes of Wolf-Hirschhorn syndrome. So far, eight NSD2 loss of function variants have been reported in patients from different parts of the world, all were de novo variants. Methods In our study, we performed whole exome sequencing for two patients from one family. We also reviewed more NSD2 mutation cases in pervious literature. Results A novel loss of function NSD2 variant, c.1577dupG (p.Asn527Lysfs*14), was identified in a Chinese family in the proband and her father both affected with intellectual disability. After reviewing more NSD2 mutation cases in pervious literature, we found none of them had facial features that can be recognized as Wolf-Hirschhorn syndrome. In addition, we have given our proband growth hormone and followed up with this family for 7.5 years. Conclusions Here we reported the first familial NSD2 variant and the long-term effect of growth hormone therapy for patients. Our results suggested NSD2 mutation might cause a distinct intellectual disability and short stature syndrome. |
topic |
Wolf-Hirschhorn syndrome NSD2 gene Growth hormone therapy Facial dysmorphism Intellectual disability |
url |
https://doi.org/10.1186/s12920-020-00831-9 |
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