Identification of BPESC1, a Novel Gene Disrupted by a Balanced Chromosomal Translocation, t(3;4)(q23;p15.2), in a Patient with BPES

Abstract

The blepharophimosis syndrome (BPES) is a rare genetic disorder characterized by blepharophimosis, ptosis, epicanthus inversus, and telecanthus. In type I, BPES is associated with female infertility, while in type II, the eyelid defect occurs by itself. The BPES syndrome has been mapped to 3q23. Previously, we constructed a YAC-, PAC-, and cosmid-based physical map surrounding the 3q23 translocation breakpoint of a t(3;4)(q23;p15.2) BPES patient, containing a 110-kb PAC (169-C 10) and a 43-kb cosmid (11-L 10) spanning the breakpoint. In this report, we present the identification of BPESC1 (BPES candidate 1), a novel candidate gene that is disrupted by the translocation on chromosome 3. Cloning of the cDNA has been performed starting from a testis-specific EST, AI032396, found in cosmid 11-L 10. The cDNA sequence of BPESC1 is 3518 bp in size and contains an open reading frame of 351 bp. No significant similarities with known proteins have been found in the sequence databases. BPESC1 contains three exons and spans a genomic fragment of 17.5 kb. Expression of BPESC1 was observed in adult testis tissue. We performed mutation analysis in 28 unrelated familial and sporadic BPES patients, but, apart from the disruption by the translocation, found no other disease-causing mutations. These data make it unlikely that BPESC1 plays a major role in the pathogenesis of BPES.

Disease-Causing 7.4 kb Cis-Regulatory Deletion Disrupting Conserved Non-Coding Sequences and Their Interaction with the FOXL2 Promotor: Implications for Mutation Screening

“…Interestingly, we identified microdeletions upstream and downstream of FOXL2 in 4% of BPES [9],[10]. In addition, 3 translocation breakpoints upstream of FOXL2 have been described [8],[11],[12]. Until now, there is no evidence for genetic heterogeneity of this condition.…”

Mental retardation, obesity, mandibular prognathism with eye and skin anomalies (MOMES Syndrome): A newly recognized autosomal recessive syndrome

“…The patient shared telecanthus, blepharophimosis and blepharoptosis with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). However, the absence of epicanthus inversus and the presence of obesity and mental retardation and its autosomal recessive inheritance do not support the diagnosis BPES [Cunniff et al, 1998;De Baere et al, 2000].…”

Blepharophimosis, Ptosis, Epicanthus Inversus Syndrome: New Report with a 197-kb Deletion Upstream of FOXL2 and Review of the Literature

“…Expression of FOXL2 is tightly regulated by distant cis -regulatory elements located both upstream and downstream of the transcription unit [Beysen et al, 2005]. The existence of 5 ′ regulatory elements was postulated even before the cloning of this gene since the breakpoints of 3 translocations in patients with BPES were found 130, 160, and 171 kb upstream of FOXL2 , respectively [De Baere et al, 2000;Praphanphoj et al, 2000;Crisponi et al, 2004]. To date, a total of 9 microdeletions upstream of FOXL2 was described in both familial and in de novo cases of BPES ( Table 2 ) [Beysen et al, 2005;D'haene et al, 2009;Verdin et al, 2013].…”