Baker K M, Olson D S, Harding C O, Pauli R M
Department of Medical Genetics, University of Wisconsin-Madison 53705, USA.
Am J Med Genet. 1997 Jun 27;70(4):427-36.
Thanatophoric dysplasia (TD), a severe skeletal dysplasia, is virtually always lethal neonatally, although a few previous reports have documented survival up to 4.75 years. We present a patient with survival beyond age 9 years and summarize his growth, development and medical history. The common Arg248Cys mutation in the extracellular region of fibroblast growth factor receptor 3 (FGFR3) was identified, eliminating the possibility that his long-term survival is attributable to an atypical mutation. This patient (and at least one other TD long-term survivor) have a rare skin disorder, acanthosis nigricans, which also occurs in Crouzon syndrome when caused by a FGFR3 mutation. Therefore, any molecular model of the origin of acanthosis nigricans secondary to FGFR3 mutations must account for the association of diverse mutations and these cutaneous effects.
致死性发育异常（TD）是一种严重的骨骼发育不良，几乎总是在新生儿期致死，尽管之前有一些报道记录了存活至4.75岁的病例。我们报告了一名存活超过9岁的患者，并总结了他的生长、发育和病史。在成纤维细胞生长因子受体3（FGFR3）细胞外区域发现了常见的Arg248Cys突变，排除了他长期存活归因于非典型突变的可能性。该患者（以及至少另一名TD长期存活者）患有罕见的皮肤疾病——黑棘皮病，当由FGFR3突变引起时，这种疾病也会出现在克鲁宗综合征中。因此，任何关于FGFR3突变继发黑棘皮病起源的分子模型都必须考虑到不同突变与这些皮肤效应之间的关联。
