A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders.
A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders.
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婴儿皮质骨质增生症（卡菲病）中的一种新的 COL1A1 突变扩大了胶原蛋白相关疾病的范围。
DOI：
10.1172/jci22760
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Jüppner,Harald
中科院分区：
文献类型：
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作者：
Gensure,RobertC;Mäkitie,Outi;Barclay,Catherine;Chan,Catherine;Depalma,StevenR;Bastepe,Murat;Abuzahra,Hilal;Couper,Richard;Mundlos,Stefan;Sillence,David;AlaKokko,Leena;Seidman,JonathanG;Cole,WilliamG;Jüppner,Harald
婴儿皮质骨质增生症(Caffey病)的特征是在出生后5个月内沿着一块或多块骨自发地形成骨膜下新骨。对一个常染色体显性遗传型Caffey病(ADC)大家族进行的全基因组遗传连锁筛查显示，染色体17q21上有一个基因座(LOD评分，6.78)。受累个体和专性携带者在编码I型胶原↠1(I)链基因第41外显子的错义突变(3040C-αT)杂合，改变了该链三螺旋结构域的836(R836C)残基。在2个无亲缘关系的ADC小家系中发现了相同的突变，但在2个产前病例中没有发现，在300多条来自健康个体的染色体中也没有发现相同的突变。患者的成纤维细胞培养产生异常的二硫键二聚体α1(I)链。同一个体的真皮胶原纤维比对照样本更大，形状和大小变化更大，密度更小。携带这种突变的个体，无论他们是否经历过皮质骨质增生症，都会出现关节过度松弛、皮肤高度伸展和腹股沟疝，这些症状类似于一种轻度的Ehler-Danlos综合征III型。这些发现扩大了COL1A1相关疾病的范围，包括一种骨质增生症。
Infantile cortical hyperostosis (Caffey disease) is characterized by spontaneous episodes of subperiosteal new bone formation along 1 or more bones commencing within the first 5 months of life. A genome-wide screen for genetic linkage in a large family with an autosomal dominant form of Caffey disease (ADC) revealed a locus on chromosome 17q21 (LOD score, 6.78). Affected individuals and obligate carriers were heterozygous for a missense mutation (3040C↠T) in exon 41 of the gene encoding the α1(I) chain of type I collagen (COL1A1), altering residue 836 (R836C) in the triple-helical domain of this chain. The same mutation was identified in affected members of 2 unrelated, smaller families with ADC, but not in 2 prenatal cases and not in more than 300 chromosomes from healthy individuals. Fibroblast cultures from an affected individual produced abnormal disulfide-bonded dimeric α1(I) chains. Dermal collagen fibrils of the same individual were larger, more variable in shape and size, and less densely packed than those in control samples. Individuals bearing the mutation, whether they had experienced an episode of cortical hyperostosis or not, had joint hyperlaxity, hyperextensible skin, and inguinal hernias resembling symptoms of a mild form of Ehlers-Danlos syndrome type III. These findings extend the spectrum ofCOL1A1-related diseases to include a hyperostotic disorder.