Evidence of postzygotic mosaicism in a transmitted form of Conradi-Hunermann-Happle syndrome associated with a novel EBP mutation.
Evidence of postzygotic mosaicism in a transmitted form of Conradi-Hunermann-Happle syndrome associated with a novel EBP mutation.
复制标题
Conradi-Hunermann-Happle 综合征传播形式的合子后嵌合与新的 EBP 突变相关的证据。
作者：
F. Morice;E. Kostrzewa;C. Wolf;P. Benlian;A. Taïeb;D. Lacombe
背景
X连锁显性点状软骨发育不良，也称为Conradi-Hünermann-Happle综合征，是一种罕见的骨骼发育不良，其特征为身材矮小、颅面缺陷、白内障、鱼鳞病、毛发粗糙和脱发。Conradi-Hünermann-Happle综合征是由编码Δ（8）-Δ（7）甾醇异构酶emopamil结合蛋白的基因EBP突变引起的。随机X失活可以解释X连锁显性点状软骨发育不良表型的家族内变异性。
意见
我们描述了一个女孩的临床特征的X连锁显性点状软骨发育不良。生化分析显示异常甾醇谱与Δ（8）-Δ（7）甾醇异构酶缺陷一致。分子生物学研究通过鉴定一种新的杂合错义EBP突变（c.199C>T; p.Cys67Arg）证实了诊断。从父母双方的血液淋巴细胞中提取的基因组DNA上未检测到突变。母亲提出了一个尖锐和鱼鳞病样皮肤病变。EBP分析从皮损皮肤活检提取的DNA显示存在p.Cys67Arg突变。
结论
据我们所知，我们报告的第一个分子确认受精后嵌合体的鱼鳞病样皮肤病变的母亲与X连锁显性点状软骨发育不良与一种新的EBP突变的女孩。
BACKGROUND
X-linked dominant chondrodysplasia punctata, also known as Conradi-Hünermann-Happle syndrome, is a rare skeletal dysplasia characterized by short stature, craniofacial defects, cataracts, ichthyosis, coarse hair, and alopecia. Conradi-Hünermann-Happle syndrome is caused by mutations in the gene EBP encoding Δ(8)-Δ(7) sterol isomerase emopamil-binding protein. Random X-inactivation could account for the intrafamilial variability of the phenotype of X-linked dominant chondrodysplasia punctata.
OBSERVATIONS
We describe a girl with clinical features of X-linked dominant chondrodysplasia punctata. Biochemical analysis showed an abnormal sterol profile consistent with a defect in Δ(8)-Δ(7) sterol isomerase. Molecular studies confirmed the diagnosis by identifying a novel heterozygous missense EBP mutation (c.199C>T; p.Cys67Arg). The mutation was not detectable on genomic DNA extracted from blood lymphocytes in both parents. The mother presented with an erythematous and ichthyosiform skin lesion. EBP analysis of DNA extracted from a lesional skin biopsy revealed the presence of p.Cys67Arg mutation.
CONCLUSION
To our knowledge, we report the first molecular confirmation of postzygotic mosaicism on an ichthyosiform skin lesion in the mother of a girl with X-linked dominant chondrodysplasia punctata associated with a novel EBP mutation.