F22 IDENTIFICATION OF TWO NEW MUTATIONS IN THE GENE RESPONSIBLE FOR THE TRICHO-RHINO-PHALANGEAL SYNDROME TYPE I

¹Seitz C. S., ²Lüdecke H.-J., ¹Wagner N., ¹Bröcker E.-B. and ¹Hamm H. ¹Department of Dermatology, University of Wuerzburg and ²Institute for Human Genetics, University Hospital Essen, Germany

The tricho-rhino-phalangeal syndrome type I (TRPS I) is a rare autosomal dominant disorder which is clinically characterized by hair changes, such as slow-growing hair and hypotrichosis, craniofacial abnormalities and skeletal deformities. Recently, the responsible gene, TRPS1 on chromosome 8q24, has been cloned.

We report one familial and one sporadic case of the TRPS I syndrome. In the familial case, mutation analysis revealed a 2480-2481 insT mutation in the TRPS1 gene leading to a premature translational stop. Careful clinical examination showed in all affected individuals sparse, slow-growing hair with tapered distal tips on microscopic examination, diffuse alopecia, a recessed fronto-temporal hairline, rarefication of lateral eyebrows, pear-shaped nose, elongated philtrum, thin upper lip, cone-shaped epiphyses of the phalanges and short stature. Additionally, they presented with a recessed triangular medio-occipital hairline and a rarefication of the eyelashes of the lower eyelids. These features have not been described in the TRPS I syndrome so far. In the sporadic case we identified a 2110 delA mutation in the TRPS1 gene leading to frameshift and premature translational stop at codon 766. The patient presented with the typical TRPS I phenotype, but in contrast to the familial case she was of normal stature.

Further clinical examination of affected individuals will show whether the recessed triangular occipital hairline and partial absence of eyelashes are distinct features of the TRPS I syndrome.