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A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly.

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A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly. / Kakar, Naseebullah; Goebel, Ingrid; Daud, Shakeela; Nürnberg, Gudrun; Agha, Noor; Ahmad, Adeel; Nürnberg, Peter; Kubisch, Christian; Ahmad, Jamil; Borck, Guntram.

In: EUR J MED GENET, Vol. 55, No. 12, 12, 2012, p. 727-731.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kakar, N, Goebel, I, Daud, S, Nürnberg, G, Agha, N, Ahmad, A, Nürnberg, P, Kubisch, C, Ahmad, J & Borck, G 2012, 'A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly.', EUR J MED GENET, vol. 55, no. 12, 12, pp. 727-731. <http://www.ncbi.nlm.nih.gov/pubmed/22989526?dopt=Citation>

APA

Kakar, N., Goebel, I., Daud, S., Nürnberg, G., Agha, N., Ahmad, A., Nürnberg, P., Kubisch, C., Ahmad, J., & Borck, G. (2012). A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly. EUR J MED GENET, 55(12), 727-731. [12]. http://www.ncbi.nlm.nih.gov/pubmed/22989526?dopt=Citation

Vancouver

Kakar N, Goebel I, Daud S, Nürnberg G, Agha N, Ahmad A et al. A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly. EUR J MED GENET. 2012;55(12):727-731. 12.

Bibtex

@article{c320360cdcfc429fa34594926c008b00,
title = "A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly.",
abstract = "Autosomal recessive intellectual disability is believed to be particularly prevalent in highly consanguineous populations and genetic isolates and may account for a quarter of all non-syndromic cases. Mutations in more than 50 genes have been reported to be involved in autosomal recessive intellectual disability, including TRAPPC9 (MIM 611966), mutations of which have been identified in six families from different geographical origins. We performed a clinical and molecular genetic study of a consanguineous Pakistani family segregating intellectual disability and microcephaly. SNP-array-based homozygosity mapping revealed suggestive linkage to four genomic regions including one on chromosome 8 that contained TRAPPC9. We detected a homozygous TRAPPC9 splice donor site mutation (c.1024+1G>T) that cosegregated with intellectual disability in the family and led to skipping of exon 3 and exons 3 and 4 in blood-derived patient RNA. We have thus identified a novel splice site mutation leading to exon skipping and premature termination of TRAPPC9 translation. These data further suggest that TRAPPC9 mutations -unlike mutations in the vast majority of the known intellectual disability-associated genes- constitute a more frequent cause of autosomal-recessive cognitive deficits, especially when microcephaly is also present.",
keywords = "Humans, Male, Female, Child, Child, Preschool, Base Sequence, Pedigree, Consanguinity, Lod Score, Chromosome Mapping, Exons, *Mutation, Carrier Proteins/*genetics, Intellectual Disability/*genetics, Facies, *Homozygote, Microcephaly/*genetics, Pakistan, *RNA Splice Sites, Humans, Male, Female, Child, Child, Preschool, Base Sequence, Pedigree, Consanguinity, Lod Score, Chromosome Mapping, Exons, *Mutation, Carrier Proteins/*genetics, Intellectual Disability/*genetics, Facies, *Homozygote, Microcephaly/*genetics, Pakistan, *RNA Splice Sites",
author = "Naseebullah Kakar and Ingrid Goebel and Shakeela Daud and Gudrun N{\"u}rnberg and Noor Agha and Adeel Ahmad and Peter N{\"u}rnberg and Christian Kubisch and Jamil Ahmad and Guntram Borck",
year = "2012",
language = "English",
volume = "55",
pages = "727--731",
journal = "EUR J MED GENET",
issn = "1769-7212",
publisher = "Elsevier Masson SAS",
number = "12",

}

RIS

TY - JOUR

T1 - A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly.

AU - Kakar, Naseebullah

AU - Goebel, Ingrid

AU - Daud, Shakeela

AU - Nürnberg, Gudrun

AU - Agha, Noor

AU - Ahmad, Adeel

AU - Nürnberg, Peter

AU - Kubisch, Christian

AU - Ahmad, Jamil

AU - Borck, Guntram

PY - 2012

Y1 - 2012

N2 - Autosomal recessive intellectual disability is believed to be particularly prevalent in highly consanguineous populations and genetic isolates and may account for a quarter of all non-syndromic cases. Mutations in more than 50 genes have been reported to be involved in autosomal recessive intellectual disability, including TRAPPC9 (MIM 611966), mutations of which have been identified in six families from different geographical origins. We performed a clinical and molecular genetic study of a consanguineous Pakistani family segregating intellectual disability and microcephaly. SNP-array-based homozygosity mapping revealed suggestive linkage to four genomic regions including one on chromosome 8 that contained TRAPPC9. We detected a homozygous TRAPPC9 splice donor site mutation (c.1024+1G>T) that cosegregated with intellectual disability in the family and led to skipping of exon 3 and exons 3 and 4 in blood-derived patient RNA. We have thus identified a novel splice site mutation leading to exon skipping and premature termination of TRAPPC9 translation. These data further suggest that TRAPPC9 mutations -unlike mutations in the vast majority of the known intellectual disability-associated genes- constitute a more frequent cause of autosomal-recessive cognitive deficits, especially when microcephaly is also present.

AB - Autosomal recessive intellectual disability is believed to be particularly prevalent in highly consanguineous populations and genetic isolates and may account for a quarter of all non-syndromic cases. Mutations in more than 50 genes have been reported to be involved in autosomal recessive intellectual disability, including TRAPPC9 (MIM 611966), mutations of which have been identified in six families from different geographical origins. We performed a clinical and molecular genetic study of a consanguineous Pakistani family segregating intellectual disability and microcephaly. SNP-array-based homozygosity mapping revealed suggestive linkage to four genomic regions including one on chromosome 8 that contained TRAPPC9. We detected a homozygous TRAPPC9 splice donor site mutation (c.1024+1G>T) that cosegregated with intellectual disability in the family and led to skipping of exon 3 and exons 3 and 4 in blood-derived patient RNA. We have thus identified a novel splice site mutation leading to exon skipping and premature termination of TRAPPC9 translation. These data further suggest that TRAPPC9 mutations -unlike mutations in the vast majority of the known intellectual disability-associated genes- constitute a more frequent cause of autosomal-recessive cognitive deficits, especially when microcephaly is also present.

KW - Humans

KW - Male

KW - Female

KW - Child

KW - Child, Preschool

KW - Base Sequence

KW - Pedigree

KW - Consanguinity

KW - Lod Score

KW - Chromosome Mapping

KW - Exons

KW - Mutation

KW - Carrier Proteins/genetics

KW - Intellectual Disability/genetics

KW - Facies

KW - Homozygote

KW - Microcephaly/genetics

KW - Pakistan

KW - RNA Splice Sites

KW - Humans

KW - Male

KW - Female

KW - Child

KW - Child, Preschool

KW - Base Sequence

KW - Pedigree

KW - Consanguinity

KW - Lod Score

KW - Chromosome Mapping

KW - Exons

KW - Mutation

KW - Carrier Proteins/genetics

KW - Intellectual Disability/genetics

KW - Facies

KW - Homozygote

KW - Microcephaly/genetics

KW - Pakistan

KW - RNA Splice Sites

M3 - SCORING: Journal article

VL - 55

SP - 727

EP - 731

JO - EUR J MED GENET

JF - EUR J MED GENET

SN - 1769-7212

IS - 12

M1 - 12

ER -