Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies

A. Hammarsjö, Z. Wang, R. Vaz, F. Taylan, M. Sedghi, K. M. Girisha, D. Chitayat, K. Neethukrishna, P. Shannon, R. Godoy, K. Gowrishankar, A. Lindstrand, J. Nasiri, M. Baktashian, P. T. Newton, L. Guo, W. Hofmeister, M. Pettersson, A. S. Chagin, G. Nishimura & 6 others L. Yan, N. Matsumoto, A. Nordgren, N. Miyake, G. Grigelioniene, S. Ikegawa

Research output: Contribution to journalArticle

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Abstract

The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA0753 gene have recently been associated with Joubert syndrome (JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in KIAA0753 in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning.

Original languageEnglish
Article number15585
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 01-12-2017

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Nonsense Codon
Orofaciodigital Syndromes
Thorax
Phenotype
Mutation
Growth Plate
Ribs
Zebrafish
Fetal Development
Genes
Cartilage
Fetus
Embryonic Structures
Bone and Bones
Ciliopathies
Joubert syndrome 1

All Science Journal Classification (ASJC) codes

  • General

Cite this

Hammarsjö, A., Wang, Z., Vaz, R., Taylan, F., Sedghi, M., Girisha, K. M., ... Ikegawa, S. (2017). Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies. Scientific Reports, 7(1), [15585]. https://doi.org/10.1038/s41598-017-15442-1
Hammarsjö, A. ; Wang, Z. ; Vaz, R. ; Taylan, F. ; Sedghi, M. ; Girisha, K. M. ; Chitayat, D. ; Neethukrishna, K. ; Shannon, P. ; Godoy, R. ; Gowrishankar, K. ; Lindstrand, A. ; Nasiri, J. ; Baktashian, M. ; Newton, P. T. ; Guo, L. ; Hofmeister, W. ; Pettersson, M. ; Chagin, A. S. ; Nishimura, G. ; Yan, L. ; Matsumoto, N. ; Nordgren, A. ; Miyake, N. ; Grigelioniene, G. ; Ikegawa, S. / Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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abstract = "The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA0753 gene have recently been associated with Joubert syndrome (JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in KIAA0753 in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning.",
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Hammarsjö, A, Wang, Z, Vaz, R, Taylan, F, Sedghi, M, Girisha, KM, Chitayat, D, Neethukrishna, K, Shannon, P, Godoy, R, Gowrishankar, K, Lindstrand, A, Nasiri, J, Baktashian, M, Newton, PT, Guo, L, Hofmeister, W, Pettersson, M, Chagin, AS, Nishimura, G, Yan, L, Matsumoto, N, Nordgren, A, Miyake, N, Grigelioniene, G & Ikegawa, S 2017, 'Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies', Scientific Reports, vol. 7, no. 1, 15585. https://doi.org/10.1038/s41598-017-15442-1

Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies. / Hammarsjö, A.; Wang, Z.; Vaz, R.; Taylan, F.; Sedghi, M.; Girisha, K. M.; Chitayat, D.; Neethukrishna, K.; Shannon, P.; Godoy, R.; Gowrishankar, K.; Lindstrand, A.; Nasiri, J.; Baktashian, M.; Newton, P. T.; Guo, L.; Hofmeister, W.; Pettersson, M.; Chagin, A. S.; Nishimura, G.; Yan, L.; Matsumoto, N.; Nordgren, A.; Miyake, N.; Grigelioniene, G.; Ikegawa, S.

In: Scientific Reports, Vol. 7, No. 1, 15585, 01.12.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies

AU - Hammarsjö, A.

AU - Wang, Z.

AU - Vaz, R.

AU - Taylan, F.

AU - Sedghi, M.

AU - Girisha, K. M.

AU - Chitayat, D.

AU - Neethukrishna, K.

AU - Shannon, P.

AU - Godoy, R.

AU - Gowrishankar, K.

AU - Lindstrand, A.

AU - Nasiri, J.

AU - Baktashian, M.

AU - Newton, P. T.

AU - Guo, L.

AU - Hofmeister, W.

AU - Pettersson, M.

AU - Chagin, A. S.

AU - Nishimura, G.

AU - Yan, L.

AU - Matsumoto, N.

AU - Nordgren, A.

AU - Miyake, N.

AU - Grigelioniene, G.

AU - Ikegawa, S.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA0753 gene have recently been associated with Joubert syndrome (JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in KIAA0753 in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning.

AB - The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA0753 gene have recently been associated with Joubert syndrome (JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in KIAA0753 in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning.

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