Dermatological phenotype in Costello syndrome: consequences of Ras dysregulation in development.
Dermatological phenotype in Costello syndrome: consequences of Ras dysregulation in development.
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DOI：
10.1111/j.1365-2133.2011.10744.x
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Rauen KA
中科院分区：
文献类型：
--
作者：
Siegel DH;Mann JA;Krol AL;Rauen KA
ras病是一类人类遗传综合征，由编码Ras/丝裂原活化蛋白激酶（MAPK）通路蛋白成分的基因发生种系突变引起。Costello综合征（CS）是一种由HRAS基因突变引起的ras病，HRAS基因是信号转导的关键调节因子。为了量化在46例确诊HRAS突变的Costello综合征患者中观察到的特定皮肤表型，这是一项横断面研究。皮肤病学调查由作者设计，并由突变阳性CS个体的父母在2007年和2009年的Costello综合征家庭网络（CSFN）会议上完成。皮肤科检查由作者在CSFN会议上进行。皮肤乳头状瘤报告33/46（71.7%）的参与者，发病年龄从婴儿期到22岁。CS患者比CFC患者更容易出现皮肤乳头状瘤（71.7%比4.9%,p<0.001）和掌足底角化皮病（76.1%比36.1%,p<0.001）。与CFC患者相比，CS患者出现眉毛稀疏或缺失的可能性更小（8.7%比90.2%,p<0.001）或毛角化症（32.6%比80.3%,p=0.001）。本研究还发现，手脚松弛、多余的皮肤、指尖8/26（31%）的“点状”皮纹（厚皮纹）和黑棘皮病17/46（37%）是CS的常见特征。虽然Ras/MAPK通路的综合征之间存在显著的表型重叠，但CS患者比CFC综合征患者更容易出现皮肤乳头状瘤、掌跖角化病和全眉，而不太可能出现发疹性红斑、毛糙角化病或多发性痣。CS是一种Ras失调综合征，其皮肤病学特征与皮肤副肿瘤综合征有许多相似之处。这可能为Ras信号在皮肤副肿瘤综合征中的作用提供进一步的见解。
The RASopathies are a class of human genetic syndromes caused by germline mutations in genes that encode protein components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Costello syndrome (CS) is a RASopathy caused by mutations in the HRAS gene, a key regulator of signal transduction. To quantify the specific cutaneous phenotype observed in 46 individuals with Costello syndrome with confirmed HRAS mutations This was a cross-sectional study. Dermatologic surveys were designed by the authors and were completed by parents of mutation-positive CS individuals at the Costello Syndrome Family Network (CSFN) conferences in 2007 and 2009. Dermatologic exams were performed by the authors at the CSFN conferences. Cutaneous papillomas are reported in 33/46 (71.7%) of participants, with age of onset ranging from infancy to 22 years. Individuals with CS are more likely than patients with cardio-facio-cutaneous syndrome (CFC) to present with cutaneous papillomas (71.7% compared to 4.9%, p<0.001) and palmoplantar keratoderma (76.1% compared to 36.1%, p<0.001). Individuals with CS are less likely than individuals with CFC to present with sparse or absent eyebrows (8.7% compared to 90.2%, p<0.001) or keratosis pilaris (32.6% compared to 80.3%, p=0.001). This study also identified that loose, redundant skin on the hands and feet, “stippled” dermatoglyphs (pachydermatoglyphia) on the fingertips 8/26 (31%), and acanthosis nigricans 17/46 (37%) are frequent features of CS. While there is significant phenotypic overlap among syndromes of the Ras/MAPK pathway, individuals with CS are more likely than individuals with CFC syndrome to present with cutaneous papillomas, palmoplantar keratoderma and full eyebrows, and are less likely to present with ulerythema ophryogenes, keratosis pilaris or multiple naevi. The dermatologic features of CS, a Ras dysregulation syndrome, share many features with cutaneous paraneoplastic syndromes. This may provide further insight into the role of Ras signaling in cutaneous paraneoplastic syndromes.
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DOI：
10.1002/ajmg.c.30294
发表时间：
2011-05-15
影响因子：
3.1
作者：
Rauen, Katherine A.;Banerjee, Anuradha;Bishop, W. Robert;Lauchle, Jennifer O.;McCormick, Frank;McMahon, Martin;Melese, Teri;Munster, Pamela N.;Nadaf, Sorena;Packer, Roger J.;Sebolt-Leopold, Judith;Viskochil, David H.
通讯作者：
Viskochil, David H.
影响因子：
64.5
作者：
BROWN, K;QUINTANILLA, M;BALMAIN, A
通讯作者：
BALMAIN, A
影响因子：
6.2
作者：
Tidyman, William E.;Rauen, Katherine A.
通讯作者：
Rauen, Katherine A.
影响因子：
2.7
作者：
COHEN, PR;GROSSMAN, ME;KURZROCK, R
通讯作者：
KURZROCK, R
影响因子：
4
作者：
Tidyman, William E.;Rauen, Katherine A.
通讯作者：
Rauen, Katherine A.