Tartaglia M, Di Rocco C, Lajeunie E, Valeri S, Velardi F, Battaglia P A
Laboratorio di Biologia Cellulare, Istituto Superiore di Sanità, Rome, Italy.
Hum Genet. 1997 Nov;101(1):47-50. doi: 10.1007/s004390050584.
Jackson-Weiss syndrome is a rare skeletal disorder characterized by craniosynostosis associated with foot malformations. This condition is inherited as an autosomal dominant trait with complete penetrance and wide phenotypic heterogeneity. Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have been recently identified as causes of this syndrome and of at least four other craniosynostotic disorders, namely the Apert, Beare-Stevenson cutis gyrata, Crouzon and Pfeiffer syndromes. We report two novel FGFR2 missense mutations associated with phenotypes consistent with Jackson-Weiss syndrome. Both nucleotide changes predict a serine for cysteine-342 substitution in the second half of the third immunoglobulin-like domain. The replacement of Cys342 with arginine has previously been reported in one of the three Jackson-Weiss cases investigated. Interestingly, both Cys342Ser and Cys342Arg substitutions have been found to be associated with the Crouzon and Pfeiffer phenotypes; a phenotypic heterogeneity, Crouzon vs Jackson-Weiss clinical features, has been also observed for Gln289Pro and Ala344Gly amino-acid changes. This finding indicates the genetic homogeneity of the "heterogeneous" Jackson-Weiss phenotype and a common molecular basis for these apparently "clinically distinct" craniosynostotic disorders.
杰克逊-韦斯综合征是一种罕见的骨骼疾病，其特征为颅缝早闭并伴有足部畸形。这种病症以常染色体显性特征遗传，具有完全外显率和广泛的表型异质性。成纤维细胞生长因子受体2（FGFR2）基因的突变最近已被确定为该综合征以及至少其他四种颅缝早闭疾病的病因，即阿佩尔综合征、比尔斯-史蒂文森回状头皮综合征、克鲁宗综合征和法伊弗综合征。我们报告了两个与符合杰克逊-韦斯综合征表型相关的新型FGFR2错义突变。这两个核苷酸变化均预测在第三个免疫球蛋白样结构域后半部分的半胱氨酸-342被丝氨酸替代。在之前研究的三例杰克逊-韦斯病例中，有一例曾报道过半胱氨酸342被精氨酸替代。有趣的是，已发现半胱氨酸342丝氨酸和半胱氨酸342精氨酸替代均与克鲁宗和法伊弗表型相关；对于谷氨酰胺289脯氨酸和丙氨酸344甘氨酸氨基酸变化，还观察到了一种表型异质性，即克鲁宗与杰克逊-韦斯临床特征的差异。这一发现表明“异质性”杰克逊-韦斯表型的遗传同质性以及这些明显“临床不同”的颅缝早闭疾病的共同分子基础。
