Molecular Vision 2005; 11:922-8 <http://www.molvis.org/molvis/v11/a110/> Received 8 March 2005 | Accepted 29 October 2005 | Published 2 November 2005 Retinitis pigmentosa (RP) is the name given to a group of hereditary retinal degeneration diseases with a worldwide incidence of about 1 in 4000 individuals [1,2]. Clinical char- acteristics include night blindness, loss of the peripheral vi- sual field, characteristic changes in the ocular fundus and de- pression of the normal ocular electrophysiological responses [3,4]. Genetically, RP is heterogeneous and the disorder may be inherited through an autosomal dominant (adRP), autoso- mal recessive (arRP), X-linked (XLRP) [5-7] or digenic trait [8]. Complex inheritance patterns such as tri-allelism [9] or uniparental disomy [10,11] have been reported. Mutations within seven genes (RHO, peripherin/RDS, ROM1, RP1, NRL, CRX, and FSCN2) that encode proteins specifically expressed in photoreceptor cells have been reported to cause adRP [12- 18]. These proteins are involved with specific functions in the retina, such as the visual transduction cycle, structural com- ponents of the rod, and cone photoreceptor cells or transcrip- tion factors. Studies of genetic linkage and mutation detection have resulted in the characterization of mutations in genes with ubiquitous expression implicated in adRP, such as the pre- mRNA splicing factors PRPF8, PRPF31, PRPF3, and PAP-1 [19-22] or the IMPDH1 and CAIV genes [23,24]. The clinical and genetic heterogeneity of RP is demonstrated by the fact that different mutations within genes associated with adRP can cause substantially different retinal degeneration pheno- types. For example, mutations within the RDS gene have been associated with RP, different forms of the macular dystrophies or the cone-rod dystrophy that is also caused by some of the mutations found in the CRX gene [25]. However, an extreme example of the clinical heterogeneity has recently been re- ported in the FSCN2 gene; the only mutation so far found in FSCN2 associated with adRP (208delG) has recently been associated with autosomal dominant macular dystrophy (adMD) in a Japanese population [18,26]. Similar heteroge- neity was seen for the mutation 1147delA in the arrestin gene in both Oguchi disease and arRP, also detected in Japanese patients and thus supporting the importance of ethnic varia- tion [27]. The photoreceptor-specific gene FSCN2, located on chro- mosome 17q25, encodes 516 amino acids [28]. Retinal fascin ©2005 Molecular Vision Sequence variations in the retinal fascin FSCN2 gene in a Spanish population with autosomal dominant retinitis pigmentosa or macular degeneration María José Gamundi, 1 Imma Hernan, 1 Miquel Maseras, 2 Montserrat Baiget, 3 Carmen Ayuso, 4 Salud Borrego, 5 Guillermo Antiñolo, 5 José María Millán, 6 Diana Valverde, 7 Miguel Carballo 1 1 Servei de Laboratori, Laboratori de Biologia i Genètica Molecular, Hospital de Terrassa, Ctra. Torrebonica, Terrassa, Spain; 2 Servei d’Oftalmologia de l’Hospital de Terrassa, Spain; 3 Servei de Genètica Molecular, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 4 Servicio de Genética, Fundación Jiménez Díaz, Madrid, Spain; 5 Servicio de Genética y Diagnóstico Prenatal, Hospital Virgen del Rocío, Sevilla, Spain; 6 Servicio de Genética, Hospital de la Fe, Valencia; 7 Área de Genética, Facultad de Ciencias, Universidad de Vigo, La Coruña, Spain Purpose: Only one mutation in the retinal fascin gene (FSCN2) has so far been associated with autosomal dominant retinitis pigmentosa (adRP) and macular dystrophy (adMD), in a Japanese population. Our study was designed to identify mutations in the FSCN2 gene among Spanish persons with adRP or adMD. Methods: Denaturing gradient gel electrophoresis and direct genomic sequencing were used to evaluate the complete coding region and flanking intronic sequences of the FSCN2 gene for mutations in 150 unrelated adRP and 15 adMD index patients, and in 50 sporadic cases of retinitis pigmentosa, together with 50 controls. Ophthalmic and electrophysi- ological examination of retinitis pigmentosa patients and their relatives was carried out according to pre-existing proto- cols. Results: Sixteen nucleotide substitutions were detected in the coding sequence of the index patients. Nine of these, His7Tyr, Ala122Thr, Ser126Phe, His138Tyr, Arg149Gln, Ala240Thr, Ala323Thr, Asn331His, and Phe367Leu are mis- sense mutations, one is a nonsense mutation (Lys302Stop), and six are silent mutations. Co-segregation of the mutations in the families showed no direct relation between mutation and disease. Conclusions: The photoreceptor-specific FSCN2 gene showed a relatively high number of sequence variations. The mutation 208delG in FSCN2, the only mutation so far associated with adRP or adMD, and which presumably causes a null allele, was not detected in these Spanish families. The nonsense mutation, Lys302Stop, detected in one adRP Spanish family is not the cause of the disease. These findings support the fact that the kind and frequency of the mutations depend on the ethnic population. Correspondence to: Miguel Carballo, Hospital de Terrassa, Carretera de Torrebonica s/n, 08227 Terrassa, Spain; Phone: +34937312420; FAX: +34937319045; e-mail: mcarballo@csdt.es 922