Przylepa K A, Paznekas W, Zhang M, Golabi M, Bias W, Bamshad M J, Carey J C, Hall B D, Stevenson R, Orlow S, Cohen M M, Jabs E W
Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Nat Genet. 1996 Aug;13(4):492-4. doi: 10.1038/ng0896-492.
Beare-Stevenson cutis gyrata syndrome (MIM 123790) is an autosomal dominant condition characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death. Many of these features are characteristic of some of the autosomal dominant craniosynostotic syndromes. Mutations in Crouzon, Jackson-Weiss, Pfeiffer and Apert syndromes have been reported in the FGFR2 extracellular domain. In Crouzon syndrome patients with acanthosis nigricans, a recurrent mutation occurs in the transmembrane domain of FGFR3. We now describe the detection of FGFR2 mutations in the Beare-Stevenson cutis gyrata syndrome. In three sporatic cases, a novel missense mutation was found causing an amino acid to be replaced by a cysteine; two had the identical Ty375Cys mutation in the transmembrane domain and one had a Ser372Cys mutation in the carboxyl-terminal end of the linker region between the immunoglobulin III-like (Iglll) and transmembrane domains. In two patients, neither of these mutations were found suggesting further genetic heterogeneity.
比厄-史蒂文森回状头皮综合征（MIM 123790）是一种常染色体显性遗传病，其特征为回状头皮的皮肤褶皱紊乱、黑棘皮病、颅缝早闭、颅面畸形、手指异常、脐部及肛门生殖器异常以及早夭。其中许多特征也是某些常染色体显性颅缝早闭综合征所具有的。据报道，在克鲁宗综合征、杰克逊-韦斯综合征、普费弗综合征和阿佩尔综合征中，FGFR2细胞外结构域存在突变。在患有黑棘皮病的克鲁宗综合征患者中，FGFR3跨膜结构域出现复发性突变。我们现在描述在比厄-史蒂文森回状头皮综合征中检测到的FGFR2突变。在3例散发病例中，发现了一种新的错义突变，导致一个氨基酸被半胱氨酸取代；其中2例在跨膜结构域有相同的Tyr375Cys突变，1例在免疫球蛋白III样（IgIII）结构域和跨膜结构域之间的连接区羧基末端有Ser372Cys突变。在2例患者中未发现这些突变，提示存在进一步的遗传异质性。
