Beijing 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 Health, Beijing, 100045, China.
Genetics and Birth Defects Control Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
BMC Med Genomics. 2020 Dec 4;13(1):181. doi: 10.1186/s12920-020-00831-9.
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.
In our study, we performed whole exome sequencing for two patients from one family. We also reviewed more NSD2 mutation cases in pervious literature.
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.
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.
沃尔夫-赫希霍恩综合征是一种由 4p16.3 缺失引起的特征明确的基因组疾病。沃尔夫-赫希霍恩综合征患者表现出特征性的面部畸形、生长迟缓、发育迟缓、智力残疾和癫痫发作障碍。最近，位于 165kb 沃尔夫-赫希霍恩综合征关键区域内的 NSD2 基因被确定为导致大多数（如果不是全部）沃尔夫-赫希霍恩综合征表型的关键致病基因。迄今为止，已有 8 种 NSD2 失活变异在来自世界各地的患者中报道，均为新生变异。
在我们的研究中，我们对来自一个家庭的两名患者进行了全外显子组测序。我们还回顾了以前文献中更多的 NSD2 突变病例。
在一个中国家庭中，在先证者及其患有智力障碍的父亲中发现了一种新的功能丧失性 NSD2 变异，c.1577dupG（p.Asn527Lysfs*14）。在回顾了以前文献中的更多 NSD2 突变病例后，我们发现没有一个病例有可被识别为沃尔夫-赫希霍恩综合征的面部特征。此外，我们已经为我们的先证者提供了生长激素，并对这个家族进行了 7.5 年的随访。
我们在这里报道了第一个家族性 NSD2 变异和生长激素治疗患者的长期效果。我们的结果表明 NSD2 突变可能导致独特的智力残疾和身材矮小综合征。
