Molecular genetic and ocular findings in patients with holt-oram syndrome.

[holt-oram syndrome]

The autosomal dominant Holt-Oram syndrome (HOS ) is characterized by upper limb and cardiac septal defects . Mutations of the TBX 5 gene have been identified as the underlying gene defect in HOS . Embryonic expression of TBX 5 has been found in the human retina . This is the first report of ocular findings in two unrelated families with mutations in the TBX 5 gene .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 ).A heterozygous single base-pain substitution in exon 5 (408 C --> 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 .Haploinsufficiency of TBX 5 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 .