IFT140 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: Intraflagellar transport 140 (Chlamydomonas) homolog
  • Subunit of intraflagellar transport (IFT) complex A
  • Ubiquitously expressed protein
  • Involved in the formation, maintenance and signaling of primary cilia
  • Critical in the development of retina and other organs
  • Dysfunction leads to ciliopathies
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
Signs for LCA/EOSRD
  • Photo-attraction
  • Hypermetropia
  • Nystagmus
  • Oculodigital sign
  • Vessel attenuation
  • Normal fundus initially but display changes over time
  • RPE disruption in the macula
  • Peripheral RPE mottling and punched out chorioretinal lesions in older patients
Signs for RP
  • Vessel attenuation
  • Diffuse, mid-peripheral white dots in the early stages
  • Progressive bone-spicule pigmentary migration over time
  • Widespread dense retinal pigmentation with retinal and RPE atrophy in advanced stages
  • Variable severity of macular atrophy
Visual function
  • Variable age of onset and severity of visual dysfunction
  • Syndromic forms tend to display severe retinal phenotype (LCA/EOSRD)
  • Nyctalopia onset typically in childhood but can occur later in life (up to the 4th decade)
  • Earlier disease onset associated with poorer visual function (LCA/EOSRD); BCVA after 5 years of age is hand motions or light perception in those with the LCA/EOSRD phenotype
  • Progressive vision loss (VF and BCVA) from 3rd to 5th decade in non-syndromic RP patients
Systemic featuresMain features
  • Skeletal anomalies (cone-shaped phalangeal epiphyses, trident-shaped spurs on the acetabular roof, constricted thoracic cage, short ribs, shortened tubular bones, polydactyly)
  • Cystic kidney disease leading to early renal failure
Additional features
  • Short stature
  • Hepatic fibrosis
  • Cerebellar ataxia
  • Mild neurodevelopmental delay
Key investigations
  • Full field ERG: rod-cone dystrophy pattern or non-recordable responses in LCA
  • Pattern ERG: subnormal or undetectable
  • FAF: Central ring of hyper-AF
  • OCT: Progressive loss of central outer retinal layers
  • Skeletal X-rays
  • Renal ultrasound
  • Systemic assessment with a paediatrician or other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
  • Multidisciplinary approach as may develop systemic manifestations later in life
Therapies under research
  • None at present
Further information

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Additional information

Homozygous or compound heterozygous mutations in IFT40 can lead to either syndromic (Jeune asphyxiating thoracic dystrophy and Mainzer-Saldino syndrome) or non-syndromic retinal dystrophies manifesting as LCA/RP. No genotype-phenotype correlations have been established at present.

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  1.  Absalon, S., Blisnick, T., Kohl, L., Toutirais, G., Dore, G., Julkowska, D., Tavenet, A., Bastin, P., 2008. Intraflagellar transport and functional analysis of genes required for flagellum formation in trypanosomes. Molecular biology of the cell 19, 929-944
  2.  Miller, K.A., Ah-Cann, C.J., Welfare, M.F., Tan, T.Y., Pope, K., Caruana, G., Freckmann, M.L., Savarirayan, R., Bertram, J.F., Dobbie, M.S., Bateman, J.F., Farlie, P.G., 2013. Cauli: a mouse strain with an Ift140 mutation that results in a skeletal ciliopathy modelling Jeune syndrome. PLoS genetics 9, e1003746
  3.  Perrault, I., Saunier, S., Hanein, S., Filhol, E., Bizet, A. A., Collins, F., Salih, M. A. M., Gerber, S., Delphin, N., Bigot, K., Orssaud, C., Silva, E., and 18 others. Mainzer-Saldino syndrome is a ciliopathy caused by IFT140 mutations. Am. J. Hum. Genet. 90: 864-870, 2012
  4.  Schmidts M, Frank V, Eisenberger T, et al. Combined NGS approaches identify mutations in the intraflagellar transport gene IFT140 in skeletal ciliopathies with early progressive kidney Disease. Hum Mutat. 2013;34(5):714-724
  5.  Bifari IN, Elkhamary SM, Bolz HJ, Khan AO. The ophthalmic phenotype of IFT140-related ciliopathy ranges from isolated to syndromic congenital retinal dystrophy. Br J Ophthalmol. 2016;100(6):829-833
  6.  Hull, S., Owen, N., Islam, F., Tracey-White, D., Plagnol, V., Holder, G.E., Michaelides, M., Carss, K., Raymond, F.L., Rozet, J.M., Ramsden, S.C., Black, G.C., Perrault, I., Sarkar, A., Moosajee, M., Webster, A.R., Arno, G., Moore, A.T., 2016. Nonsyndromic Retinal Dystrophy due to Bi-Allelic Mutations in the Ciliary Transport Gene IFT140. Invest. Ophthalmol. Vis. Sci. 57, 1053-1062
  7.  Xu, M., Yang, L., Wang, F., Li, H., Wang, X., Wang, W., Ge, Z., Wang, K., Zhao, L., Li, H., Li, Y., Sui, R., Chen, R., 2015. Mutations in human IFT140 cause non-syndromic retinal degeneration. Hum. Genet. 134, 1069-1078
  8.  Beheshtian, M., Saee Rad, S., Babanejad, M., Mohseni, M., Hashemi, H., Eshghabadi, A., Hajizadeh, F., Akbari, M.R., Kahrizi, K., Riazi Esfahani, M., Najmabadi, H., 2015. Impact of whole exome sequencing among Iranian patients with autosomal recessive retinitis pigmentosa. Arch. Iran. Med. 18, 776-785

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Updated on November 30, 2020
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