A novel splice-site mutation of TULP1 underlies severe early-onset retinitis pigmentosa in a consanguineous Israeli Muslim Arab family.
OBJECTIVE
To investigate the genetic basis for autosomal recessive severe early-onset retinitis pigmentosa (RP) in a consanguineous Israeli Muslim Arab family.


METHODS
Haplotype analysis for all known genes underlying autosomal recessive RP was performed. Mutation screening of the underlying gene was done by direct sequencing. An in vitro splicing assay was used to evaluate the effect of the identified mutation on splicing.


RESULTS
Haplotype analysis indicated linkage to the Tubby-like protein 1 (TULP)1 gene. Direct sequencing revealed a homozygous single base insertion, c.1495+2_1495+3insT, located in the conserved donor splice-site of intron 14. This mutation co-segregated with the disease, and was not detected in 114 unrelated Israeli Muslim Arab controls. We used an in vitro splicing assay to demonstrate that this mutation leads to incorrect splicing.


CONCLUSIONS
To date, 22 distinct pathogenic mutations of TULP1 have been reported in patients with early-onset RP or Leber congenital amaurosis. Here we report a novel splice-site mutation of TULP1, c.1495+2_1495+3insT, underlying autosomal recessive early-onset RP in a consanguineous Israeli Muslim Arab family. This report expands the spectrum of pathogenic mutations of the TULP1 gene.
Abbasi
Anan H
AH
Department of Genetics and The Rappaport Family Institute for Research in the Medical Sciences, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Garzozi
Hanna J
HJ
Ben-Yosef
Tamar
T
D000328:Adult; D017668:Age of Onset; D000368:Aged; D018912:Arabs / Q000235:genetics*; D001483:Base Sequence; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D005654:Fundus Oculi; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D007514:Islam; D007557:Israel / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000453:epidemiology* / Q000235:genetics*
D005136:Eye Proteins; D022821:RNA Splice Sites; C105443:TULP1 protein, human