Tags

Type your tag names separated by a space and hit enter

Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism.
Hum Mutat. 2012 Oct; 33(10):1429-34.HM

Abstract

Primordial dwarfism (PD) is a clinically and genetically heterogeneous condition. Various molecular mechanisms are known to underlie the disease including impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA damage response, defective spliceosomal machinery, and abnormal replication licensing. Here, we describe a syndromic form of PD associated with severe intellectual disability and distinct facial features in a large multiplex Saudi family. Analysis reveals a novel underlying mechanism for PD involving depletion of 7SK, an abundant cellular noncoding RNA (ncRNA), due to mutation of its chaperone LARP7. We show that 7SK levels are tightly linked to LARP7 expression across cell lines, and that this chaperone is ubiquitously expressed in the mouse embryo. The 7SK is known to influence the expression of a wide array of genes through its inhibitory effect on the positive transcription elongation factor b (P-TEFb) as well as its competing role in HMGA1-mediated transcriptional regulation. This study documents a critical role played by ncRNA in human development and adds to the growing list of molecular mechanisms that, when perturbed, converge on the PD phenotype.

Authors+Show Affiliations

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22865833

Citation

Alazami, Anas M., et al. "Loss of Function Mutation in LARP7, Chaperone of 7SK ncRNA, Causes a Syndrome of Facial Dysmorphism, Intellectual Disability, and Primordial Dwarfism." Human Mutation, vol. 33, no. 10, 2012, pp. 1429-34.
Alazami AM, Al-Owain M, Alzahrani F, et al. Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism. Hum Mutat. 2012;33(10):1429-34.
Alazami, A. M., Al-Owain, M., Alzahrani, F., Shuaib, T., Al-Shamrani, H., Al-Falki, Y. H., Al-Qahtani, S. M., Alsheddi, T., Colak, D., & Alkuraya, F. S. (2012). Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism. Human Mutation, 33(10), 1429-34. https://doi.org/10.1002/humu.22175
Alazami AM, et al. Loss of Function Mutation in LARP7, Chaperone of 7SK ncRNA, Causes a Syndrome of Facial Dysmorphism, Intellectual Disability, and Primordial Dwarfism. Hum Mutat. 2012;33(10):1429-34. PubMed PMID: 22865833.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism. AU - Alazami,Anas M, AU - Al-Owain,Mohammad, AU - Alzahrani,Fatema, AU - Shuaib,Taghreed, AU - Al-Shamrani,Hussain, AU - Al-Falki,Yahya H, AU - Al-Qahtani,Saleh M, AU - Alsheddi,Tarfa, AU - Colak,Dilek, AU - Alkuraya,Fowzan S, Y1 - 2012/08/30/ PY - 2012/03/30/received PY - 2012/07/19/accepted PY - 2012/8/7/entrez PY - 2012/8/7/pubmed PY - 2013/7/6/medline SP - 1429 EP - 34 JF - Human mutation JO - Hum Mutat VL - 33 IS - 10 N2 - Primordial dwarfism (PD) is a clinically and genetically heterogeneous condition. Various molecular mechanisms are known to underlie the disease including impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA damage response, defective spliceosomal machinery, and abnormal replication licensing. Here, we describe a syndromic form of PD associated with severe intellectual disability and distinct facial features in a large multiplex Saudi family. Analysis reveals a novel underlying mechanism for PD involving depletion of 7SK, an abundant cellular noncoding RNA (ncRNA), due to mutation of its chaperone LARP7. We show that 7SK levels are tightly linked to LARP7 expression across cell lines, and that this chaperone is ubiquitously expressed in the mouse embryo. The 7SK is known to influence the expression of a wide array of genes through its inhibitory effect on the positive transcription elongation factor b (P-TEFb) as well as its competing role in HMGA1-mediated transcriptional regulation. This study documents a critical role played by ncRNA in human development and adds to the growing list of molecular mechanisms that, when perturbed, converge on the PD phenotype. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/22865833/Loss_of_function_mutation_in_LARP7_chaperone_of_7SK_ncRNA_causes_a_syndrome_of_facial_dysmorphism_intellectual_disability_and_primordial_dwarfism_ L2 - https://doi.org/10.1002/humu.22175 DB - PRIME DP - Unbound Medicine ER -