Hemati Parisa, du Souich Christèle, Boerkoel Cornelius F
Child and Family Research Institute, Vancouver, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Am J Med Genet A. 2015 Jan;167A(1):231-7. doi: 10.1002/ajmg.a.36821. Epub 2014 Oct 29.
Chromosome 4q deletion syndrome is a rare intellectual disability disorder caused by a variety of non-recurrent deletions of 4q. We describe the evolution of the phenotypic features of a female patient with a previously unreported deletion of 4q12-4q21.21 (hg 18; 54,711,575-79,601,919). By review reported individuals with interstitial deletions extending telomeric from 4q12 have syndromic intellectual disability with variable piebaldism. We expand the phenotype to include dolichocephaly, pectus excavatum, hip dysplasia, pes planus, myopia, lens opacities, and an absence of spoken language but not of communication through sign. The proposita also did not have piebaldism suggesting again that piebaldism arises from a mechanism more complex than simple haploinsufficiency of KIT. Comparing deletions among affected individuals localizes the critical interval within 4q12-4q13.1, although the absence of molecular boundaries for nearly all reported cases precludes precise delineation and genotype-phenotype correlation.
4号染色体长臂缺失综合征是一种由4号染色体长臂多种非重复性缺失引起的罕见智力残疾疾病。我们描述了一名女性患者的表型特征演变情况，该患者存在先前未报道的4q12 - 4q21.21（hg 18；54,711,575 - 79,601,919）缺失。通过回顾报道的4q12端粒延伸的间质性缺失个体，发现他们患有综合征性智力残疾，并伴有不同程度的花斑病。我们进一步扩展了该综合征的表型，包括长头畸形、漏斗胸、髋关节发育不良、扁平足、近视、晶状体混浊，以及无语言表达但能通过手势进行交流。先证者也没有花斑病，这再次表明花斑病的发生机制比单纯的KIT单倍剂量不足更为复杂。比较受影响个体的缺失情况，将关键区间定位在4q12 - 4q13.1内，尽管几乎所有报道病例都没有分子边界，这妨碍了精确的界定以及基因型与表型的相关性分析。
