Identification of novel mutations in the SEMA4A gene associated with retinal degenerative diseases

• Published in: Journal of medical genetics Vol. 43; no. 4; pp. 378 - 381
• Main Authors: Abid, A, Ismail, M, Mehdi, S Q, Khaliq, S
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.04.2006; BMJ Publishing Group LTD; BMJ Group
• Subjects: Amino acids; Blindness - congenital; Blindness - diagnosis; Blindness - genetics; Blood vessels; cone rod dystrophy; Conserved Sequence; CRD; CRD, cone rod dystrophy; DNA Mutational Analysis; Female; Genetic Testing; Humans; LCA; LCA, Leber congenital amaurosis; Leber congenital amaurosis; Letter to JMG; Letters to JMG; Male; Mutation; Mutation, Missense; Pedigree; Photoreceptors; Proteins; retinal degeneration; retinal pigment epithelial; retinitis pigmentosa; Retinitis Pigmentosa - diagnosis; Retinitis Pigmentosa - genetics; RP, retinitis pigmentosa; RPE; RPE, retinal pigment epithelial; SEMA4A; Semaphorins - chemistry; Semaphorins - genetics; single stranded conformational polymorphism; SSCP; SSCP, single stranded conformational polymorphism
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2005.035055

Semaphorins are a large family of transmembrane proteins. The gene for SEMA4A encodes a transmembrane protein comprising 760 amino acids. To investigate its association with human retinal degeneration, mutation screening of the SEMA4A gene was carried out on 190 unrelated patients suffering from a variety of eye diseases. We report the first observation of the involvement of SEMA4A gene mutations causing retinitis pigmentosa (RP) and cone rod dystrophy (CRD). We screened the DNA of 135 patients with RP, 25 patients with CRD, and 30 with LCA using SSCP and direct DNA sequencing for mutations in the SEMA4A gene. Two mutations, p.D345H and p.F350C, were observed only in affected patients; they were not observed in any of the normal members or the 100 control subjects. Both mutations identified occur in the conserved semaphorin domain. Multiple sequence alignments using Clustal analysis showed that R713Q is a conserved substitution and D345H is a semi-conserved substitution. We conclude that these mutations are a cause of various retinal degenerations.