Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1
Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1
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DOI：
10.1086/516843
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发表时间：
2007-05-01
影响因子：
9.8
通讯作者：
Rutsch, Frank
中科院分区：
文献类型：
--
作者：
Crisponi, Laura;Crisponi, Giangiorgio;Rutsch, Frank
克里斯波尼综合征是一种严重的常染色体隐性遗传疾病，其表型特征为异常的阵发性肌肉收缩，类似新生儿破伤风，大脸，宽鼻，前倾鼻孔，驼趾，体温过高，多数病例猝死。我们利用高密度单核苷酸多态芯片对5个患有Crisponi综合征的撒丁人和3个土耳其家系进行了纯合子定位，并确定了染色体19p12-13.1上的一个关键区域。最突出的候选基因是CRLF1，最近发现它与冷汗综合征1型(CISS1)的发病机制有关。CisS1属于一组表型重叠的疾病，还包括冷汗综合征2型和Stuve-Wiedemann综合征。所有这些综合征都是由睫状神经营养因子(CNTF)受体途径基因突变引起的。在这里，我们描述了在8个不同的Crisponi影响家系中鉴定出四种不同的CRLF1突变，包括错义突变、单核苷酸插入、无义和插入/缺失(INDel)突变，所有这些突变都与家系的疾病特征分离。对Crisponi综合征和Crisponi综合征突变谱的比较表明，CRLF1突变的类型和位置都不指向可能解释Crisponi综合征最严重表型的表型/基因型相关性。其他尚不清楚的分子因素可能是CRLF1突变的可变表型表达的原因。我们认为这些综合征可以包括一个“CNTF受体相关疾病”家族，其中Crisponi综合征将是最新的成员和等位基因。
Crisponi syndrome is a severe autosomal recessive condition that is phenotypically characterized by abnormal, paroxysmal muscular contractions resembling neonatal tetanus, large face, broad nose, anteverted nares, camptodactyly, hyperthermia, and sudden death in most cases. We performed homozygosity mapping in five Sardinian and three Turkish families with Crisponi syndrome, using high-density single-nucleotide polymorphism arrays, and identified a critical region on chromosome 19p12-13.1. The most prominent candidate gene was CRLF1, recently found to be involved in the pathogenesis of cold-induced sweating syndrome type 1 (CISS1). CISS1 belongs to a group of conditions with overlapping phenotypes, also including cold-induced sweating syndrome type 2 and Stuve-Wiedemann syndrome. All these syndromes are caused by mutations of genes of the ciliary neurotrophic factor ( CNTF) - receptor pathway. Here, we describe the identification of four different CRLF1 mutations in eight different Crisponi-affected families, including a missense mutation, a single-nucleotide insertion, and a nonsense and an insertion/deletion (indel) mutation, all segregating with the disease trait in the families. Comparison of the mutation spectra of Crisponi syndrome and CISS1 suggests that neither the type nor the location of the CRLF1 mutations points to a phenotype/genotype correlation that would account for the most severe phenotype in Crisponi syndrome. Other, still-unknown molecular factors may be responsible for the variable phenotypic expression of the CRLF1 mutations. We suggest that the syndromes can comprise a family of "CNTF-receptor - related disorders," of which Crisponi syndrome would be the newest member and allelic to CISS1.