Chan I, Hamada T, Hardman C, McGrath J A, Child F J
Department of Dermatology, St Mary's Hospital, London, UK.
Clin Exp Dermatol. 2004 Jan;29(1):77-80. doi: 10.1111/j.1365-2230.2004.01439.x.
Progressive osseous heteroplasia (OMIM 166350) is a rare autosomal dominant condition that presents in childhood as dermal ossification and may progress deeper to involve subcutaneous fat and connective tissue. Recently, paternally inherited inactivating mutations in the GNAS1 gene on chromosome 20q13 have been implicated in the pathogenesis, although sporadic cases have also been reported. We report a 9-year-old British Chinese girl with progressive osseous heteroplasia resulting from a de novo missense mutation (W281R) in the GNAS1 gene. She is of small stature (0.4th centile) and started to develop skin lesions at the age of 9 months. These have been confirmed histologically as osteoma cutis. She is of normal intelligence and development and has no dysmorphic features. The GNAS1 gene exhibits imprinting and maternally inherited mutations have previously been shown to result in Albright's hereditary osteodystrophy (OMIM 103580) with pseudohypothyroidism type 1a, whereas paternally inherited mutations result in progressive osseous heteroplasia or the Albright's hereditary osteodystrophy phenotype with pseudopseudohypothyroidism (OMIM 300800). With only nine mutations of the GNAS1 gene reported so far in progressive osseous heteroplasia, this new mutation helps to extend further the genotype-phenotype correlation.
进行性骨化性纤维发育不良（OMIM 166350）是一种罕见的常染色体显性疾病，在儿童期表现为皮肤骨化，且可能向深部发展累及皮下脂肪和结缔组织。最近，20q13染色体上GNAS1基因的父系遗传失活突变被认为与发病机制有关，尽管也有散发病例的报道。我们报告了一名9岁的英籍华裔女孩，她因GNAS1基因的新发错义突变（W281R）而患有进行性骨化性纤维发育不良。她身材矮小（第0.4百分位），9个月大时开始出现皮肤病变，经组织学证实为皮肤骨瘤。她智力和发育正常，没有畸形特征。GNAS1基因表现出印记现象，先前已表明母系遗传突变会导致伴有1a型假性甲状旁腺功能减退的奥尔布赖特遗传性骨营养不良（OMIM 103580），而父系遗传突变会导致进行性骨化性纤维发育不良或伴有假性假性甲状旁腺功能减退的奥尔布赖特遗传性骨营养不良表型（OMIM 300800）。由于迄今为止在进行性骨化性纤维发育不良中仅报道了9个GNAS1基因的突变，这个新突变有助于进一步扩展基因型与表型的相关性。
