CONCISE COMMUNICATION DOI 10.1111/j.1365-2133.2007.08158.x Missense mutation in exon 7 of TRPS1 gene in an Italian family with a mild form of trichorhinophalangeal syndrome type I A. Rossi, V. Devirgiliis, V. Panasiti, R.G. Borroni, M. Carlesimo, M. Gentile,* F. Cariola* and S. Calvieri Department of Dermatology, ‘La Sapienza’ University, Viale del Policlinico, 155, 00161 Rome, Italy *UOC Genetica Medica – ASL BA ⁄ 04, Bari, Italy Correspondence Vincenzo Panasiti. E-mail: ilcapo75@gmx.net Accepted for publication 1 July 2007 Key words autosomal dominant disorder, trichorhinophalangeal syndrome, TRPS1 gene Conflicts of interest None declared. Summary Background Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant disorder, three types of which have been described in the literature. All of them are characterized by alopecia, facial dysmorphism and bone deformities. Dele- tions and nonsense mutations of the TRPS1 gene are responsible for most of the TRPS I and III cases with no clear genotype–phenotype correlation. The majority of missense mutations have been described at TRPS1 exon 6, encoding a pre- sumptive GATA DNA-binding domain, and are known to be associated with the most severe forms of the phenotypic spectrum of TRPS. Mutation mapping at exon 7 described to date includes nonsense mutations and a familial case with an insertion mutation. Objectives To determine a possible correlation between a mutation at exon 7 and mild TRPS phenotype. Methods We describe three members of an Italian family with TRPS I. All three showed clinical features typical of TRPS I such as temporal alopecia and facial abnormalities, but no mental retardation. Results Mutation analysis showed a missense mutation (R952C) in exon 7 of the TRPS1 gene. Conclusions R952C is the first missense mutation described outside the GATA zinc- finger domain of TRPS1. In contrast with missense mutations occurring within this region, this mutation prevents the transport of the TRPS1 protein into the nucleus, therefore determining TRPS I by haploinsufficiency. We hypothesize that a TRPS exon 7 mutation could result in a mild phenotype. Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant disorder, 1 three types of which have been described in the literature, all characterized by alopecia, facial dysmor- phism and bone deformities 2 (Table 1). The responsible gene TRPS1 has been identified on chromo- some 8q24.1 and encodes a zinc-finger transcription factor. 3 Mutations of TRPS1 account for the majority of TRPS I and III cases (86%) with no clear genotype–phenotype correl- ation. 4 The only exception is probably represented by TRPS III, a TRPS I variant characterized by more severe brachydac- tyly and growth retardation, which is often caused by a spe- cific class of TRPS1 gene mutations. 5,6 We report here a family affected by TRPS I. The clinical and molecular data are discussed in light of reported findings, in order to find a possible correlation between this kind of muta- tion and a mild TRPS phenotype. Patients and methods Patient 1 A 14-year-old girl was referred to our Department of Derma- tology in 1996 because of thin, slow-growing hair and alope- cia. Family history included the same alopecia in her father and in her brother. Physical examination revealed facial pallor, low-set ears bilaterally, bulbous distal nose, slightly elongated philtrum, thin upper lip and prognathism (Fig. 1a); mild brachydactyly, valgus knee and flatfoot were also present. Thin scalp hair was particularly evident in the frontoparietal regions; receding frontotemporal hairline and rarefaction of lateral eyebrows were also present (Fig. 1b). Her height was 150 cm (> 25th centile) and weight 45Æ4 kg (50th centile). Her mental and motor development was normal. Radiological Ó 2007 The Authors Journal Compilation Ó 2007 British Association of Dermatologists • British Journal of Dermatology 2007 157, pp1021–1024 1021