患有不同程度脑异常的成骨不全症兄弟姐妹中WNT1最5'端截短的纯合突变：一例报告
The most 5' truncating homozygous mutation of WNT1 in siblings with osteogenesis imperfecta with a variable degree of brain anomalies: a case report.
作者信息
Kuptanon Chulaluck, Srichomthong Chalurmpon, Sangsin Apiruk, Kovitvanitcha Dool, Suphapeetiporn Kanya, Shotelersuk Vorasuk
机构信息
Department of Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, 10400, Thailand.
Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
出版信息
BMC Med Genet. 2018 Jul 16;19(1):117. doi: 10.1186/s12881-018-0639-0.
BACKGROUND
WNT1 mutations cause bone fragility as well as brain anomalies. There are some reported cases of WNT1 mutations with normal cognition. Genotype and phenotype correlation of WNT1 mutations has not been established.
CASE PRESENTATION
Here we present two female siblings with osteogenesis imperfecta (OI) born to a consanguineous couple. Both sustained severe bone deformities. However, only the younger had severe brain anomalies resulting in an early death from pneumonia, while the older had normal intellectual development. Next generation sequencing showed a homozygous mutation, c.6delG, p.Leu3Serfs*36 in WNT1. To our knowledge, it is the most 5' truncating mutation to date.
CONCLUSION
This report emphasizes the intrafamilial variability of brain anomalies found in this OI type and suggests that WNT1 may not be necessary for normal human cognitive development.
背景
WNT1突变会导致骨骼脆弱以及脑部异常。有一些报道的WNT1突变病例认知功能正常。WNT1突变的基因型与表型相关性尚未确立。
病例报告
在此，我们报告一对近亲结婚夫妇所生的患有成骨不全症（OI）的女性姐妹。两人均患有严重的骨骼畸形。然而，只有年幼的妹妹有严重的脑部异常，最终因肺炎早夭，而年长的姐姐智力发育正常。下一代测序显示WNT1基因存在纯合突变，即c.6delG，p.Leu3Serfs*36。据我们所知，这是迄今为止最靠近5'端的截短突变。
结论
本报告强调了这种类型的成骨不全症中脑部异常存在家族内变异性，并表明WNT1可能并非人类正常认知发育所必需。
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