Rosenfeld Jill A, Lacassie Yves, El-Khechen Dima, Escobar Luis F, Reggin James, Heuer Carolyn, Chen Emily, Jenkins Lauren S, Collins A Thomas, Zinner Samuel, Babcock Melanie, Morrow Bernice, Schultz Roger A, Torchia Beth S, Ballif Blake C, Tsuchiya Karen D, Shaffer Lisa G
Signature Genomic Laboratories, 2820 N. Astor St., Spokane, WA 99207, USA.
Eur J Med Genet. 2011 Jan-Feb;54(1):42-9. doi: 10.1016/j.ejmg.2010.10.002. Epub 2010 Oct 15.
Microdeletions of 1q41q42 have recently been classified as a syndrome. Features include significant developmental delay and characteristic dysmorphic features as well as cleft palate, clubfeet, seizures, and short stature in some individuals, with a clinical diagnosis of Fryns syndrome in two individuals with congenital diaphragmatic hernia at the severe end of the spectrum. The gene DISP1, which is involved in sonic hedgehog signaling, has been proposed as a candidate for the midline defects in this syndrome. We undertook a genotype-phenotype analysis of seven previously unreported individuals with deletions of 1q41q42 that range from 777 kb to 6.87 Mb. Three of the individuals in our cohort do not display the major features of the syndrome and have more proximal deletions that only overlap with the previously described 1q41q42 smallest region of overlap (SRO) at DISP1. One individual with several features of the syndrome has a more distal deletion that excludes DISP1. The three remaining individuals have larger deletions that include the entire SRO and demonstrate features of the microdeletion syndrome. Confounding genotype-phenotype correlations, one of the small deletions involving DISP1 was inherited from a phenotypically normal parent. DISP1 haploinsufficiency may not be solely responsible for the major features of 1q41q42 microdeletion syndrome, and other genes in the SRO likely play a role in the phenotype. Additionally, some features present in a minority of individuals, such as Pelger-Huët anomaly, may be attributed to deletions of genes outside of the SRO.
1q41q42微缺失最近被归类为一种综合征。其特征包括显著的发育迟缓、特征性的畸形特征，以及部分个体出现腭裂、马蹄内翻足、癫痫发作和身材矮小，在该综合征谱系严重端的两名患有先天性膈疝的个体中临床诊断为弗林斯综合征。参与音猬因子信号传导的DISP1基因被认为是该综合征中线缺陷的候选基因。我们对7名先前未报告的1q41q42缺失个体进行了基因型-表型分析，缺失范围从777 kb到6.87 Mb。我们队列中的3名个体未表现出该综合征的主要特征，其缺失更靠近近端，仅在DISP1处与先前描述的1q41q42最小重叠区域（SRO）重叠。一名具有该综合征若干特征的个体有更远端的缺失，不包括DISP1。其余3名个体有更大的缺失，包括整个SRO，并表现出微缺失综合征的特征。混淆基因型-表型相关性的是，其中一个涉及DISP1的小缺失是从表型正常的父母遗传而来。DISP1单倍体不足可能并非1q41q42微缺失综合征主要特征的唯一原因，SRO中的其他基因可能在表型中起作用。此外，少数个体中出现的一些特征，如Pelger-Huët异常，可能归因于SRO以外基因的缺失。
