Molecular genetic and ocular findings in patients with holt-oram syndrome.
OBJECTIVE
The autosomal dominant Holt-Oram syndrome (HOS) is characterized by upper limb and cardiac septal defects. Mutations of the TBX5 gene have been identified as the underlying gene defect in HOS. Embryonic expression of TBX5 has been found in the human retina. This is the first report of ocular findings in two unrelated families with mutations in the TBX5 gene.


METHODS
Six living persons affected with HOS and 10 unaffected family members were subjected to mutation analysis and complete ophthalmological examination, including electrophysiological examinations (EOG and flash ERG).


RESULTS
A heterozygous single base-pain substitution in exon 5 (408C --> A) was detected in all affected patients. All examined affected patents were ophthalmological asymptomatic with normal EOG. A scotopic elongated b-wave latency was found in affected family members who were older than 35 years. The ERG was normal in the young patients.


CONCLUSIONS
Haploinsufficiency of TBX5 alters the dorsal-ventral polarity in developing eye vesicles without amy detected functional loss in human. Slight ERG abnormalities later in life may be a result of changes induced by the inner ganglion cell layer in the inner nuclear layer.
Gruenauer-Kloevekorn
Claudia
C
Department of Opthalmology, Martin-Luther-University, Halle, Germany. cup-gk@t-online.de
Reichel
Martin B
MB
Duncker
G I W
GI
Froster
Ursula G
UG
D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D003941:Diagnostic Techniques, Ophthalmological; D004585:Electrooculography; D004596:Electroretinography; D005260:Female; D005799:Genes, Dominant; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome; D020825:T-Box Domain Proteins / Q000235:genetics*; D038062:Upper Extremity Deformities, Congenital / Q000235:genetics*; D014792:Visual Acuity
D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5