The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1

Dan Hanson; Philip G. Murray; Amit Sud; Samia A. Temtamy; Mona Aglan; Andrea Superti-Furga; Sue E. Holder; Jill Urquhart; Emma Hilton; Forbes D C Manson; Peter Scambler; Graeme C M Black; Peter E. Clayton

doi:10.1016/j.ajhg.2009.04.021

The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1

Dan Hanson, Philip G. Murray, Amit Sud, Samia A. Temtamy, Mona Aglan, Andrea Superti-Furga, Sue E. Holder, Jill Urquhart, Emma Hilton, Forbes D C Manson, Peter Scambler, Graeme C M Black, Peter E. Clayton

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

Abstract

3-M syndrome is an autosomal-recessive primordial growth disorder characterized by significant intrauterine and postnatal growth restriction. Mutations in the CUL7 gene are known to cause 3-M syndrome. In 3-M syndrome patients that do not carry CUL7 mutations, we performed high-density genome-wide SNP mapping to identify a second locus at 2q35-q36.1. Further haplotype analysis revealed a 1.29 Mb interval in which the underlying gene is located and we subsequently discovered seven distinct null mutations from 10 families within the gene OBSL1. OBSL1 is a putative cytoskeletal adaptor protein that localizes to the nuclear envelope. We were also able to demonstrate that loss of OBSL1 leads to downregulation of CUL7, implying a role for OBSL1 in the maintenance of CUL7 protein levels and suggesting that both proteins are involved within the same molecular pathway. © 2009 The American Society of Human Genetics.

Original language	English
Pages (from-to)	801-806
Number of pages	5
Journal	American Journal of Human Genetics
Volume	84
Issue number	6
DOIs	https://doi.org/10.1016/j.ajhg.2009.04.021
Publication status	Published - 12 Jun 2009

Keywords

Adolescent
Cells, Cultured
Child
Child, Preschool
genetics: Cullin Proteins
antagonists & inhibitors: Cytoskeletal Proteins
Cytoskeleton
Female
genetics: Growth Disorders
Humans
Infant
cytology: Kidney
Male
genetics: Mutation
Oligonucleotide Array Sequence Analysis
Pedigree
genetics: Polymorphism, Single Nucleotide
pharmacology: RNA, Small Interfering
Syndrome
Ubiquitination

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10.1016/j.ajhg.2009.04.021

Defining the phenotype of severe growth disorders, discovering new genes that control human growth and enhancing clinical practice
Clayton, P. (Participant), Black, G. (Participant), Read, A. (Participant), Manson, F. (Participant), Hanson, D. (Participant) & Patel, L. (Participant)
Impact: Health impacts

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Hanson, D., Murray, P. G., Sud, A., Temtamy, S. A., Aglan, M., Superti-Furga, A., Holder, S. E., Urquhart, J., Hilton, E., Manson, F. D. C., Scambler, P., Black, G. C. M., & Clayton, P. E. (2009). The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1. American Journal of Human Genetics, 84(6), 801-806. https://doi.org/10.1016/j.ajhg.2009.04.021

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title = "The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1",

abstract = "3-M syndrome is an autosomal-recessive primordial growth disorder characterized by significant intrauterine and postnatal growth restriction. Mutations in the CUL7 gene are known to cause 3-M syndrome. In 3-M syndrome patients that do not carry CUL7 mutations, we performed high-density genome-wide SNP mapping to identify a second locus at 2q35-q36.1. Further haplotype analysis revealed a 1.29 Mb interval in which the underlying gene is located and we subsequently discovered seven distinct null mutations from 10 families within the gene OBSL1. OBSL1 is a putative cytoskeletal adaptor protein that localizes to the nuclear envelope. We were also able to demonstrate that loss of OBSL1 leads to downregulation of CUL7, implying a role for OBSL1 in the maintenance of CUL7 protein levels and suggesting that both proteins are involved within the same molecular pathway. {\textcopyright} 2009 The American Society of Human Genetics.",

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author = "Dan Hanson and Murray, {Philip G.} and Amit Sud and Temtamy, {Samia A.} and Mona Aglan and Andrea Superti-Furga and Holder, {Sue E.} and Jill Urquhart and Emma Hilton and Manson, {Forbes D C} and Peter Scambler and Black, {Graeme C M} and Clayton, {Peter E.}",

year = "2009",

month = jun,

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doi = "10.1016/j.ajhg.2009.04.021",

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journal = "American Journal of Human Genetics",

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Hanson, D, Murray, PG, Sud, A, Temtamy, SA, Aglan, M, Superti-Furga, A, Holder, SE, Urquhart, J, Hilton, E , Manson, FDC, Scambler, P, Black, GCM & Clayton, PE 2009, 'The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1', American Journal of Human Genetics, vol. 84, no. 6, pp. 801-806. https://doi.org/10.1016/j.ajhg.2009.04.021

TY - JOUR

T1 - The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1

AU - Hanson, Dan

AU - Murray, Philip G.

AU - Sud, Amit

AU - Temtamy, Samia A.

AU - Aglan, Mona

AU - Superti-Furga, Andrea

AU - Holder, Sue E.

AU - Urquhart, Jill

AU - Hilton, Emma

AU - Manson, Forbes D C

AU - Scambler, Peter

AU - Black, Graeme C M

AU - Clayton, Peter E.

PY - 2009/6/12

Y1 - 2009/6/12

N2 - 3-M syndrome is an autosomal-recessive primordial growth disorder characterized by significant intrauterine and postnatal growth restriction. Mutations in the CUL7 gene are known to cause 3-M syndrome. In 3-M syndrome patients that do not carry CUL7 mutations, we performed high-density genome-wide SNP mapping to identify a second locus at 2q35-q36.1. Further haplotype analysis revealed a 1.29 Mb interval in which the underlying gene is located and we subsequently discovered seven distinct null mutations from 10 families within the gene OBSL1. OBSL1 is a putative cytoskeletal adaptor protein that localizes to the nuclear envelope. We were also able to demonstrate that loss of OBSL1 leads to downregulation of CUL7, implying a role for OBSL1 in the maintenance of CUL7 protein levels and suggesting that both proteins are involved within the same molecular pathway. © 2009 The American Society of Human Genetics.

AB - 3-M syndrome is an autosomal-recessive primordial growth disorder characterized by significant intrauterine and postnatal growth restriction. Mutations in the CUL7 gene are known to cause 3-M syndrome. In 3-M syndrome patients that do not carry CUL7 mutations, we performed high-density genome-wide SNP mapping to identify a second locus at 2q35-q36.1. Further haplotype analysis revealed a 1.29 Mb interval in which the underlying gene is located and we subsequently discovered seven distinct null mutations from 10 families within the gene OBSL1. OBSL1 is a putative cytoskeletal adaptor protein that localizes to the nuclear envelope. We were also able to demonstrate that loss of OBSL1 leads to downregulation of CUL7, implying a role for OBSL1 in the maintenance of CUL7 protein levels and suggesting that both proteins are involved within the same molecular pathway. © 2009 The American Society of Human Genetics.

KW - Adolescent

KW - Cells, Cultured

KW - Child

KW - Child, Preschool

KW - genetics: Cullin Proteins

KW - antagonists & inhibitors: Cytoskeletal Proteins

KW - Cytoskeleton

KW - Female

KW - genetics: Growth Disorders

KW - Humans

KW - Infant

KW - cytology: Kidney

KW - Male

KW - genetics: Mutation

KW - Oligonucleotide Array Sequence Analysis

KW - Pedigree

KW - genetics: Polymorphism, Single Nucleotide

KW - pharmacology: RNA, Small Interfering

KW - Syndrome

KW - Ubiquitination

U2 - 10.1016/j.ajhg.2009.04.021

DO - 10.1016/j.ajhg.2009.04.021

M3 - Article

C2 - 19481195

SN - 0002-9297

VL - 84

SP - 801

EP - 806

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 6

ER -

The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1

Abstract

Keywords

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Impacts

Defining the phenotype of severe growth disorders, discovering new genes that control human growth and enhancing clinical practice

Cite this