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

Jacquelyn Bond; Sheila Scott; Daniel J. Hampshire; Kelly Springell; Peter Corry; Marc J. Abramowicz; Ganesh H. Mochida; Raoul C. M. Hennekam; Eamonn R. Maher; Jean-Pierre Fryns; Abdulrahman Alswaid; Hussain Jafri; Yasmin Rashid; Ammar Mubaidin; Christopher A. Walsh; Emma Roberts

doi:10.1086/379085

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

Jacquelyn Bond, Sheila Scott, Daniel J. Hampshire, Kelly Springell, Peter Corry, Marc J. Abramowicz, Ganesh H. Mochida, Raoul C. M. Hennekam, Eamonn R. Maher, Jean-Pierre Fryns, Abdulrahman Alswaid, Hussain Jafri, Yasmin Rashid, Ammar Mubaidin, Christopher A. Walsh, Emma Roberts

Aston Medical School

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

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	English
Pages (from-to)	1170-7
Number of pages	8
Journal	American Journal of Human Genetics
Volume	73
Issue number	5
DOIs	https://doi.org/10.1086/379085
Publication status	Published - Nov 2003

Keywords

Amino Acid Sequence
Base Sequence
Brain/abnormalities
Chromosomes, Human, Pair 1/genetics
Codon, Nonsense/genetics
Consanguinity
DNA Mutational Analysis
Exons/genetics
Frameshift Mutation/genetics
Genes, Recessive/genetics
Haplotypes/genetics
Humans
Intellectual Disability/complications
Introns/genetics
Male
Microcephaly/complications
Microsatellite Repeats/genetics
Mutation/genetics
Nerve Tissue Proteins/genetics
Pakistan
Phenotype
Polymorphism, Genetic/genetics
RNA, Messenger/genetics

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10.1086/379085

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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. (2003). Protein-truncating mutations in ASPM cause variable reduction in brain size. American Journal of Human Genetics, 73(5), 1170-7. https://doi.org/10.1086/379085

@article{58f6c8a5c08d44fab383e36d4986766d,

title = "Protein-truncating mutations in ASPM cause variable reduction in brain size",

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.",

keywords = "Amino Acid Sequence, Base Sequence, Brain/abnormalities, Chromosomes, Human, Pair 1/genetics, Codon, Nonsense/genetics, Consanguinity, DNA Mutational Analysis, Exons/genetics, Frameshift Mutation/genetics, Genes, Recessive/genetics, Haplotypes/genetics, Humans, Intellectual Disability/complications, Introns/genetics, Male, Microcephaly/complications, Microsatellite Repeats/genetics, Mutation/genetics, Nerve Tissue Proteins/genetics, Pakistan, Phenotype, Polymorphism, Genetic/genetics, RNA, Messenger/genetics",

author = "Jacquelyn Bond and Sheila Scott and Hampshire, {Daniel J.} and Kelly Springell and Peter Corry and Abramowicz, {Marc J.} and Mochida, {Ganesh H.} and Hennekam, {Raoul C. M.} and Maher, {Eamonn R.} and Jean-Pierre Fryns and Abdulrahman Alswaid and Hussain Jafri and Yasmin Rashid and Ammar Mubaidin and Walsh, {Christopher A.} and Emma Roberts",

year = "2003",

month = nov,

doi = "10.1086/379085",

language = "English",

volume = "73",

pages = "1170--7",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "5",

}

Bond, J, Scott, S, Hampshire, DJ, Springell, K, Corry, P, Abramowicz, MJ, Mochida, GH, Hennekam, RCM, Maher, ER, Fryns, J-P, Alswaid, A, Jafri, H, Rashid, Y, Mubaidin, A, Walsh, CA & Roberts, E 2003, 'Protein-truncating mutations in ASPM cause variable reduction in brain size', American Journal of Human Genetics, vol. 73, no. 5, pp. 1170-7. https://doi.org/10.1086/379085

TY - JOUR

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

AU - Bond, Jacquelyn

AU - Scott, Sheila

AU - Hampshire, Daniel J.

AU - Springell, Kelly

AU - Corry, Peter

AU - Abramowicz, Marc J.

AU - Mochida, Ganesh H.

AU - Hennekam, Raoul C. M.

AU - Maher, Eamonn R.

AU - Fryns, Jean-Pierre

AU - Alswaid, Abdulrahman

AU - Jafri, Hussain

AU - Rashid, Yasmin

AU - Mubaidin, Ammar

AU - Walsh, Christopher A.

AU - Roberts, Emma

PY - 2003/11

Y1 - 2003/11

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 - Amino Acid Sequence

KW - Base Sequence

KW - Brain/abnormalities

KW - Chromosomes, Human, Pair 1/genetics

KW - Codon, Nonsense/genetics

KW - Consanguinity

KW - DNA Mutational Analysis

KW - Exons/genetics

KW - Frameshift Mutation/genetics

KW - Genes, Recessive/genetics

KW - Haplotypes/genetics

KW - Humans

KW - Intellectual Disability/complications

KW - Introns/genetics

KW - Male

KW - Microcephaly/complications

KW - Microsatellite Repeats/genetics

KW - Mutation/genetics

KW - Nerve Tissue Proteins/genetics

KW - Pakistan

KW - Phenotype

KW - Polymorphism, Genetic/genetics

KW - RNA, Messenger/genetics

UR - https://www.sciencedirect.com/science/article/pii/S000292970761979X

U2 - 10.1086/379085

DO - 10.1086/379085

M3 - Article

C2 - 14574646

SN - 0002-9297

VL - 73

SP - 1170

EP - 1177

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 5

ER -

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

Abstract

Keywords

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