Abstract
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.
Highlights
Blepharoptosis, usually abbreviated to the term ptosis, is defined as the abnormal drooping of the upper eyelid
The condition can be familial and we have previously carried out linkage analysis on a UK pedigree with dominantly inherited congenital bilateral isolated ptosis which indicated that the causative locus lay within a critical region of approximately 20 Mb of Xq24-27.1 which has since been refined to a region of 18 Mb [1]
We have identified an unbalanced insertional duplication of approximately 120 kb of the dihydropyrimidine dehydrogenase (DPYD) gene on chromosome 1p21.3 into Xq27.1, der (X) dir ins (X;1) (q27.1;p21.3), in a family with X linked dominant congenital bilateral isolated ptosis
Summary
Blepharoptosis, usually abbreviated to the term ptosis, is defined as the abnormal drooping of the upper eyelid. It can be bilateral or unilateral, congenital or acquired, in isolated or syndromic form and is a feature of many conditions. The condition can be familial and we have previously carried out linkage analysis on a UK pedigree with dominantly inherited congenital bilateral isolated ptosis which indicated that the causative locus lay within a critical region of approximately 20 Mb of Xq24-27.1 which has since been refined to a region of 18 Mb [1]. X-linked ptosis has been seen in other families as part of a much broader phenotype which included microcephaly and digital defects [3], but the candidate genes proposed in those families, FAM45B and ENOX2, are 6 Mb outside of our linkage region
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