Mundlos S, Otto F, Mundlos C, Mulliken J B, Aylsworth A S, Albright S, Lindhout D, Cole W G, Henn W, Knoll J H, Owen M J, Mertelsmann R, Zabel B U, Olsen B R
Kinderklinik, Klinikum der Johannes-Gutenberg-Universität, Mainz, Germany.
Cell. 1997 May 30;89(5):773-9. doi: 10.1016/s0092-8674(00)80260-3.
Cleidocranial dysplasia (CCD) is an autosomal-dominant condition characterized by hypoplasia/aplasia of clavicles, patent fontanelles, supernumerary teeth, short stature, and other changes in skeletal patterning and growth. In some families, the phenotype segregates with deletions resulting in heterozygous loss of CBFA1, a member of the runt family of transcription factors. In other families, insertion, deletion, and missense mutations lead to translational stop codons in the DNA binding domain or in the C-terminal transactivating region. In-frame expansion of a polyalanine stretch segregates in an affected family with brachydactyly and minor clinical findings of CCD. We conclude that CBFA1 mutations cause CCD and that heterozygous loss of function is sufficient to produce the disorder.
锁骨颅骨发育不全（CCD）是一种常染色体显性疾病，其特征为锁骨发育不全/发育不全、囟门未闭、多生牙、身材矮小以及骨骼形态和生长的其他变化。在一些家族中，该表型与导致转录因子 runt 家族成员 CBFA1 杂合性缺失的缺失相关。在其他家族中，插入、缺失和错义突变导致 DNA 结合域或 C 末端反式激活区域出现翻译终止密码子。一个多聚丙氨酸序列的框内扩增在一个患有短指症和 CCD 轻微临床症状的患病家族中分离。我们得出结论，CBFA1 突变导致 CCD，并且功能的杂合性丧失足以产生该疾病。
