Analysis of FOXL2 detects three novel mutations and an atypical phenotype of blepharophimosis-ptosis-epicanthus inversus syndrome.
Clin Exp Ophthalmol
; 44(9): 757-762, 2016 Dec.
Article
em En
| MEDLINE
| ID: mdl-27283035
ABSTRACT
BACKGROUND:
Mutations in FOXL2 are known to cause autosomal dominant blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), variably associated with premature ovarian failure. In this study, we report results of mutational screening in a Czech and Slovak patient population with BPES.DESIGN:
Case series.PARTICIPANTS:
Thirteen probands of Czech and one proband of Slovak origin with BPES and their available family members.METHODS:
Sanger sequencing and multiplex ligation-dependent probe amplification in 14 probands with BPES. Targeted mutational screening in first-degree relatives. MAIN OUTCOMEMEASURES:
Genetic characterization and phenotype evaluation in Czech and Slovak individuals with BPES and their family members.RESULTS:
Eight different mutations were detected including three novel ones c.5T>G; p.(Met2Arg), c.197C>A; p.(Ala66Glu) and c.701_702insTGCAGCCGCAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC; p.(Ala222_Ala234dup). In one family, the molecular genetic cause of disease was not identified by the methodology used. In 13 pedigrees, a negative family history suggested a de novo origin, which could be confirmed by targeted mutational screening in four families. One 62-year-old female with the c.663_692dup30 mutation had an atypical phenotype presenting as moderate ptosis compensated by frontalis muscle contraction, no epicanthus inversus and no premature ovarian failure.CONCLUSIONS:
The de novo mutation rate in FOXL2 is exceptionally high compared with other dominant disorders manifesting with an ocular phenotype. In cases reporting a negative family history, careful examination of both parents is important to exclude mild features of the BPES phenotype.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Anormalidades da Pele
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Anormalidades Urogenitais
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Blefarofimose
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Mutação de Sentido Incorreto
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Fatores de Transcrição Forkhead
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article