Murray Mitzi L, Yang Margaret, Fauth Christine, Byers Peter H
Department of Pathology, University of Washington, Seattle, Washington; Department of Medicine (Medical Genetics), University of Washington, Seattle, Washington.
Am J Med Genet A. 2014 Jul;164A(7):1750-5. doi: 10.1002/ajmg.a.36492. Epub 2014 Mar 26.
Biallelic mutations in FKBP14 cause a recessive form of Ehlers-Danlos syndrome (EDS) characterized by progressive kyphoscoliosis, myopathy, and hearing loss. To date, four children and one adult with this condition have been reported. We recently identified a 42-year-old man with severe kyphoscoliosis, restrictive/obstructive lung disease, short stature, mild hearing loss, decreased muscle mass, and a dissection of the celiac artery at age 41. He also had complete occlusion of the superior mesenteric artery with compensatory flow through an enlarged and tortuous inferior mesenteric artery. He was homozygous for a previously identified FKBP14 mutation, c.362dupC, p.(Glu122Argfs*7). He had no mutations in COL3A1, ACTA2, TGFBR1, TGFBR2, or SMAD3. The FKBP14 mutations in our patient occurred on the same haplotype as others with this same mutation. Although one family member in a previous report was thought to have early vascular complications, it could not be confirmed that she had biallelic mutations in FKBP14. This report expands the phenotype of FKBP14-related EDS to include risk for vascular complications and also raises the question of whether the shared haplotype represents a risk allele or founder mutation.
FKBP14基因的双等位基因突变会导致一种隐性的埃勒斯-当洛综合征（EDS），其特征为进行性脊柱后凸侧弯、肌病和听力丧失。迄今为止，已有4名儿童和1名成人被报道患有这种疾病。我们最近鉴定出一名42岁男性，患有严重的脊柱后凸侧弯、限制性/阻塞性肺病、身材矮小、轻度听力丧失、肌肉量减少，并且在41岁时发生了腹腔动脉夹层。他还存在肠系膜上动脉完全闭塞，通过增粗迂曲的肠系膜下动脉实现代偿性血流。他对于先前鉴定出的FKBP14突变c.362dupC、p.(Glu122Argfs*7)呈纯合状态。他在COL3A1、ACTA2、TGFBR1、TGFBR2或SMAD3基因中没有突变。我们患者中的FKBP14突变与其他具有相同突变的患者发生在相同的单倍型上。尽管先前报道中的一名家庭成员被认为有早期血管并发症，但无法证实她在FKBP14基因中有双等位基因突变。本报告将FKBP14相关EDS的表型扩展至包括血管并发症风险，同时也提出了共享单倍型是代表风险等位基因还是奠基者突变的问题。
