[Mutation analysis of FOXL2 in Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndrome].

OBJECTIVE

To identify the genetic mutation in two Chinese families and 6 sporadic patients with belpharophimosis-ptosis-epicanthus inversus syndrome (BPES).

METHODS

Polymorphisms of 5 satellite markers on 3q were analyzed and linkage analysis was performed using linkage software (MLINK) in all cases of two families. FOXL2 gene fragments were amplified by PCR and mutation was determined by sequencing DNA fragments in all patients.

RESULTS

The BPES locus in the pedigrees was mapped to 3q23, a 9.88 cM interval between markers D3S3696 and D3S1744. The maximum lod scores were 2.11 (theta = 0.00) at D3S1549 and D3S3586 and 1.51 (theta = 0.00) at D3S1764. By direct sequencing FOXL2 gene, two sporadic cases had a 30-bp in frame duplication 909 - 938 dup 30 and one sporadic case showed a nucleotide insertion 1041 - 1042 ins C. However, it was unable to find any causal mutation of FOXL2 in two families with BPES.

CONCLUSIONS

The gene responsible for BPES in two Chinese families was linked to D3S1549, D3S3586 and D3S1764. This is the first reported mutations of FOXL2 (909 - 938 dup 30 and 1041 - 1042 ins C) in Chinese sporadic cases. One of the mutations, in-frame 30-bp duplication (909 - 938 dup 30), is one of the most common mutation hotspots in the coding region of FOXL2. In BPES families without FOXL2 mutation, it cannot be excluded that the disorder is caused by a position effect in the surrounding region of FOXL2 gene or by other genes located at 3q23.