Chun K, Siegel-Bartelt J, Chitayat D, Phillips J, Ray P N
Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Med Genet. 1998 May 18;77(3):219-24. doi: 10.1002/(sici)1096-8628(19980518)77:3<219::aid-ajmg6>3.0.co;2-k.
The Antley-Bixler syndrome (ABS) is a rare syndrome with synostosis of cranial sutures and elbow joints as minimal diagnostic criteria. The inheritance has been suggested to be autosomal recessive based on two families with sib recurrence with both sexes being affected, and two cases born to consanguineous parents. We report the first case of ABS associated with an apparent dominant de novo mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. The patient was found to be heterozygous for a C-->G transversion at nucleotide 1064, which predicts a Ser351Cys amino acid substitution in the IgIII domain of FGFR2. Apart from the craniosynostosis and elbow ankylosis, our patient also presented with severe spinal dysraphism, the first report of such a finding in association with ABS. This suggests that FGFR2 is expressed as early as the fourth week of embryogenesis when somite formation occurs. We propose that the Antley-Bixler syndrome is an autosomal dominant condition with possible gonadal mosaicism. Alternatively, there may be two types of ABS: an autosomal dominant form and an autosomal recessive form. In light of our findings, FGFR mutations should be looked for in other craniosynostosis patients with elbow synostosis.
安特利-比克斯勒综合征（ABS）是一种罕见综合征，其诊断标准为颅缝和肘关节融合。基于两个同胞复发且男女均受累的家族以及两例近亲结婚父母所生病例，推测其遗传方式为常染色体隐性遗传。我们报告了首例与成纤维细胞生长因子受体2（FGFR2）基因显性新发突变相关的ABS病例。患者在核苷酸1064处存在C→G颠换的杂合子，这预测FGFR2的IgIII结构域中会出现Ser351Cys氨基酸替换。除颅缝早闭和肘关节强直外，我们的患者还出现了严重的脊柱裂，这是与ABS相关的此类发现的首例报告。这表明FGFR2早在胚胎发育第四周体节形成时就已表达。我们认为安特利-比克斯勒综合征是一种常染色体显性疾病，可能存在生殖腺嵌合体。或者，可能有两种类型的ABS：常染色体显性形式和常染色体隐性形式。鉴于我们的发现，对于其他伴有肘关节融合的颅缝早闭患者应检测FGFR突变。
