Comparative analysis of the FOXL2 gene and characterization of mutations in BPES patients
| Autor: | Rosamaria Silva-Garcia, Nitin Udar, S. Yelchits, Meenal Chalukya, Vivek S. Yellore, Kent W. Small |
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| Rok vydání: | 2003 |
| Předmět: |
Forkhead Box Protein L2
Male Molecular Sequence Data Pedigree chart Biology Blepharophimosis Conserved sequence FOXL2 Gene Mice Genetics Coding region Animals Blepharoptosis Humans Abnormalities Multiple Amino Acid Sequence Gene Genetics (clinical) Conserved Sequence Mice Inbred ICR Fugu Ovary Forkhead Transcription Factors Syndrome Pedigree Takifugu DNA-Binding Proteins Mice Inbred C57BL Mutation Mutation testing Female Transcription Factor Gene Transcription Factors |
| Zdroj: | Human mutation. 22(3) |
| ISSN: | 1098-1004 |
| Popis: | Bleparophimosis ptosis epicanthus inversus syndrome (BPES) is a rare disorder characterized by eyelid malformation and in some cases associated with premature ovarian failure. Although the familial form is autosomal dominant, many cases are also sporadic. The mutations causing this disorder were found in a winged/forkhead transcription factor gene named FOXL2. We have sequenced the mouse homolog for the FOXL2 gene and identified the Fugu rubripes (pufferfish) ortholog from the database. By alignment of the three sequences, we found an almost complete conservation of the forkhead domain in the three species. There is 95% and 61% conservation at the protein level between human–mouse and human–pufferfish, respectively. The polyalanine and polyproline tracts within the gene are absent in Fugu rubripes. An overview identifies four breaks in the conservation of the gene within these species. Using a direct sequencing approach, we performed mutation analysis from DNA of nine affected individuals from familial and sporadic cases. The mutations are distributed throughout the coding region of the FOXL2 gene. We identified five novel mutations: g.292delG (E19fsX149); g.530G>A (W98X); g.548A>G (H104R); g.652G>T (E139X); and g.1178underscore;1185del8 (A314fsX530). In addition we also identified two known mutations g.823C>T (Q196X) and g.1092underscore;1108dup17, the latter in individuals from three unrelated pedigrees. Hum Mutat 22:222–228, 2003. © 2003 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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