Article which may be of interest (relating to Type 1, Type 2)

[Guest guest]

I would recommend that people in the group who are interested in this

subject ask their genetics advisor to get hold of the full text of

this article and ask them to discuss it with you.

Shireen

~~~~~~~~~~~

From the American Journal of Medical Genetics

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Research Article

FOXL2-mutations in blepharophimosis-ptosis - epicanthus inversus

syndrome (BPES); challenges for genetic counseling in female patients

Siv Fokstuen *, Stylianos E. Antonarakis, Jean-Louis Blouin

Division of Medical Genetics, University of Geneva Medical School and

University Hospitals, Geneva, Switzerland

email: Siv Fokstuen (siv.fokstuen@...)

*Correspondence to Siv Fokstuen, Division of Medical Genetics,

University of Geneva Medical School, 1 rue Michel-Servet, CH-1211

Geneva.

Keywords

Blepharophimosis-ptosis-epicanthus inversus syndrome • FOXL2

•

genetic counseling • female fertility

Abstract

Mutations in the forkhead transcription factor gene 2 (FOXL2) were

recently reported to cause blepharophimosis-ptosis-epicanthus

inversus syndrome (BPES) types I and II. Evidence was provided that

BPES type I (eyelid abnormalities and female infertility) is caused

by mutations resulting in a truncated FOXL2 protein. In contrast,

mutant FOXL2 proteins, either with inserted aminoacids in the

forkhead domain or polyalanine tract, or with novel aminoacids at the

carboxyl end, were found in BPES type II, in which fertility is

generally normal. We report a 32-year-old female patient with

sporadic BPES and a history of menstrual cycle irregularities and

periods of secondary amenorrhoea. A heterozygous frameshift mutation

(c959-960insG) was found in the FOXL2 gene, resulting in a predicted

FOXL2 protein with 212 novel aminoacids in the carboxyl end,

suggesting BPES type II despite menstrual irregularities. The

clinical presentations of our patient and of three female patients

with BPES type II in the report of De Baere et al. [2001: Hum Mol

Genet 10:1591-1600.] indicate phenotypic overlap between BPES type I

and II. These observations do not support a clear-cut prediction of

female fertility based on the FOXL2 molecular defect. As a

consequence, FOXL2 mutation testing in female patients of child-

bearing age with BPES should be handled with caution, and a two-step

genetic counseling approach, including an initial pre-test

information session, is proposed. © 2003 Wiley-Liss, Inc.