X-Linked Dominant Congenital Ptosis Cosegregating with an Interstitial Insertion of a Chromosome 1p21.3 Fragment into a Quasipalindromic Sequence in Xq27.1

作     者：David J. Bunyan David O. Robinson Anthony G. Tyers Shuwen Huang Vivienne K. Maloney Francis H. Grand Sarah Ennis Samantha R. de Silva John A. Crolla Tristan F. W. McMullan 

作者机构：Wessex Regional Genetics Laboratory Salisbury District Hospital Salisbury UK Human Genetics Division Southampton University School of Medicine Southampton UK Ophthalmology Department Salisbury District Hospital Salisbury UK Manchester Centre for Genomic Medicine Saint Mary’s Hospital Manchester UK Genetic Epidemiology and Genomic Informatics Group Faculty of Medicine University of SouthamptonSouthampton UK Oxford Eye Hospital John Radcliffe Hospital Oxford UK Ophthalmology Department Northampton General Hospital Northampton UK 

出 版 物：《Open Journal of Genetics》 (遗传学期刊（英文）)

年 卷 期：2014年第4卷第6期

页      面：415-425页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Ptosis X-Linked Dominant Insertional Duplication 

摘      要：Blepharoptosis (ptosis) is defined as the abnormal drooping of the upper eyelid and is a feature of many conditions. It can be in isolated or syndromic form, bilateral or unilateral and congenital or acquired. Previously we have carried out linkage analysis on a family with dominantly inherited congenital bilateral isolated ptosis and found the condition to be linked to a region of approximately 20 megabases of chromosome Xq24-Xq27.1 with a cumulative LOD score of 5.89. We now describe further analysis using array comparative genomic hybridisation (array CGH), fluorescence in situ hybridisation (FISH), long range PCR and sequencing. This has enabled us to identify and characterise at the level of DNA sequence an insertional duplication and rearrangement involving chromosomes 1p21.3 and a small quasipalindromic sequence in Xq27.1, disruption of which has been associated with other phenotypes but which is cosegregating with X-linked congenital bilateral isolated ptosis in this family. This work highlights the significance of the small quasipalindromic sequence in genomic rearrangements involving Xq27.1 and the importance of comprehensive molecular and molecular cytogenetic investigations to fully characterise genomic structural complexity.