Protein-truncating mutations in ASPM cause variable reduction in brain size

J. Bond; S. Scott; D.J. Hampshire; K. Springell; P. Corry; M.J. Abramowicz; G.H. Mochida; R.C.M. Hennekam; E.R. Maher; J.P. Fryns; A. Alswaid; H. Jafri; Y. Rashid; A. Mubaidin; C.A. Walsh; E. Roberts; C.G. Woods

doi:https://doi.org/10.1086/379085

Protein-truncating mutations in ASPM cause variable reduction in brain size

J. Bond, S. Scott, D.J. Hampshire, K. Springell, P. Corry, M.J. Abramowicz, G.H. Mochida, R.C.M. Hennekam, E.R. Maher, J.P. Fryns, A. Alswaid, H. Jafri, Y. Rashid, A. Mubaidin, C.A. Walsh, E. Roberts, C.G. Woods

Paediatric Genetics (AMC)

Research output: Contribution to journal › Article › Academic › peer-review

152 Citations (Scopus)

Abstract

Mutations in the ASPM gene at the MCPH5 locus are expected to be the most common cause of human autosomal recessive primary microcephaly (MCPH), a condition in which there is a failure of normal fetal brain development, resulting in congenital microcephaly and mental retardation. We have performed the first comprehensive mutation screen of the 10.4-kb ASPM gene, identifying all 19 mutations in a cohort of 23 consanguineous families. Mutations occurred throughout the ASPM gene and were all predicted to be protein truncating. Phenotypic variation in the 51 affected individuals occurred in the degree of microcephaly (5-11 SDs below normal) and of mental retardation (mild to severe) but appeared independent of mutation position

Original language	Undefined/Unknown
Pages (from-to)	1170-1177
Journal	American journal of human genetics
Volume	73
Issue number	5
DOIs	https://doi.org/10.1086/379085
Publication status	Published - 2003

Keywords

AMC wi-buiten

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https://doi.org/10.1086/379085

https://pure.uva.nl/ws/files/3415750/33248_143476y.pdf

Cite this

Bond, J., Scott, S., Hampshire, D. J., Springell, K., Corry, P., Abramowicz, M. J., Mochida, G. H., Hennekam, R. C. M., Maher, E. R., Fryns, J. P., Alswaid, A., Jafri, H., Rashid, Y., Mubaidin, A., Walsh, C. A., Roberts, E., & Woods, C. G. (2003). Protein-truncating mutations in ASPM cause variable reduction in brain size. American journal of human genetics, 73(5), 1170-1177. https://doi.org/10.1086/379085

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abstract = "Mutations in the ASPM gene at the MCPH5 locus are expected to be the most common cause of human autosomal recessive primary microcephaly (MCPH), a condition in which there is a failure of normal fetal brain development, resulting in congenital microcephaly and mental retardation. We have performed the first comprehensive mutation screen of the 10.4-kb ASPM gene, identifying all 19 mutations in a cohort of 23 consanguineous families. Mutations occurred throughout the ASPM gene and were all predicted to be protein truncating. Phenotypic variation in the 51 affected individuals occurred in the degree of microcephaly (5-11 SDs below normal) and of mental retardation (mild to severe) but appeared independent of mutation position",

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author = "J. Bond and S. Scott and D.J. Hampshire and K. Springell and P. Corry and M.J. Abramowicz and G.H. Mochida and R.C.M. Hennekam and E.R. Maher and J.P. Fryns and A. Alswaid and H. Jafri and Y. Rashid and A. Mubaidin and C.A. Walsh and E. Roberts and C.G. Woods",

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Bond, J, Scott, S, Hampshire, DJ, Springell, K, Corry, P, Abramowicz, MJ, Mochida, GH, Hennekam, RCM, Maher, ER, Fryns, JP, Alswaid, A, Jafri, H, Rashid, Y, Mubaidin, A, Walsh, CA, Roberts, E & Woods, CG 2003, 'Protein-truncating mutations in ASPM cause variable reduction in brain size', American journal of human genetics, vol. 73, no. 5, pp. 1170-1177. https://doi.org/10.1086/379085

TY - JOUR

T1 - Protein-truncating mutations in ASPM cause variable reduction in brain size

AU - Bond, J.

AU - Scott, S.

AU - Hampshire, D.J.

AU - Springell, K.

AU - Corry, P.

AU - Abramowicz, M.J.

AU - Mochida, G.H.

AU - Hennekam, R.C.M.

AU - Maher, E.R.

AU - Fryns, J.P.

AU - Alswaid, A.

AU - Jafri, H.

AU - Rashid, Y.

AU - Mubaidin, A.

AU - Walsh, C.A.

AU - Roberts, E.

AU - Woods, C.G.

PY - 2003

Y1 - 2003

N2 - Mutations in the ASPM gene at the MCPH5 locus are expected to be the most common cause of human autosomal recessive primary microcephaly (MCPH), a condition in which there is a failure of normal fetal brain development, resulting in congenital microcephaly and mental retardation. We have performed the first comprehensive mutation screen of the 10.4-kb ASPM gene, identifying all 19 mutations in a cohort of 23 consanguineous families. Mutations occurred throughout the ASPM gene and were all predicted to be protein truncating. Phenotypic variation in the 51 affected individuals occurred in the degree of microcephaly (5-11 SDs below normal) and of mental retardation (mild to severe) but appeared independent of mutation position

AB - Mutations in the ASPM gene at the MCPH5 locus are expected to be the most common cause of human autosomal recessive primary microcephaly (MCPH), a condition in which there is a failure of normal fetal brain development, resulting in congenital microcephaly and mental retardation. We have performed the first comprehensive mutation screen of the 10.4-kb ASPM gene, identifying all 19 mutations in a cohort of 23 consanguineous families. Mutations occurred throughout the ASPM gene and were all predicted to be protein truncating. Phenotypic variation in the 51 affected individuals occurred in the degree of microcephaly (5-11 SDs below normal) and of mental retardation (mild to severe) but appeared independent of mutation position

KW - AMC wi-buiten

U2 - https://doi.org/10.1086/379085

DO - https://doi.org/10.1086/379085

M3 - Article

C2 - 14574646

SN - 0002-9297

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SP - 1170

EP - 1177

JO - American journal of human genetics

JF - American journal of human genetics

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