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Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families.
J Med Genet 2010; 47(12):797-802JM

Abstract

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II, MIM 210720) and Seckel syndrome (SCKL, MIM 210600) belong to the primordial dwarfism group characterised by intrauterine growth retardation, severe proportionate short stature, and pronounced microcephaly. MOPD II is distinct from SCKL by more severe growth retardation, radiological abnormalities, and absent or mild mental retardation. Seckel syndrome is associated with defective ATR dependent DNA damage signalling. In 2008, loss-of-function mutations in the pericentrin gene (PCNT) have been identified in 28 patients, including 3 SCKL and 25 MOPDII cases. This gene encodes a centrosomal protein which plays a key role in the organisation of mitotic spindles. The aim of this study was to analyse PCNT in a large series of SCKL-MOPD II cases to further define the clinical spectrum associated with PCNT mutations. Among 18 consanguineous families (13 SCKL and 5 MOPDII) and 6 isolated cases (3 SCKL and 3 MOPD II), 13 distinct mutations were identified in 5/16 SCKL and 8/8 MOPDII including five stop mutations, five frameshift mutations, two splice site mutations, and one apparent missense mutation affecting the last base of exon 19. Moreover, we demonstrated that this latter mutation leads to an abnormal splicing with a predicted premature termination of translation. The clinical analysis of the 5 SCKL cases with PCNT mutations showed that they all presented minor skeletal changes and clinical features compatible with MOPDII diagnosis. It is therefore concluded that, despite variable severity, MOPDII is a genetically homogeneous condition due to loss-of-function of pericentrin.

Authors+Show Affiliations

Department of Genetics, Université Paris Descartes, INSERM U781, Necker Hospital, 149 rue de Sèvres, 75015 Paris, France.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 availableNo 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 availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19643772

Citation

Willems, M, et al. "Molecular Analysis of Pericentrin Gene (PCNT) in a Series of 24 Seckel/microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II) Families." Journal of Medical Genetics, vol. 47, no. 12, 2010, pp. 797-802.
Willems M, Geneviève D, Borck G, et al. Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. J Med Genet. 2010;47(12):797-802.
Willems, M., Geneviève, D., Borck, G., Baumann, C., Baujat, G., Bieth, E., ... Cormier-Daire, V. (2010). Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. Journal of Medical Genetics, 47(12), pp. 797-802. doi:10.1136/jmg.2009.067298.
Willems M, et al. Molecular Analysis of Pericentrin Gene (PCNT) in a Series of 24 Seckel/microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II) Families. J Med Genet. 2010;47(12):797-802. PubMed PMID: 19643772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. AU - Willems,M, AU - Geneviève,D, AU - Borck,G, AU - Baumann,C, AU - Baujat,G, AU - Bieth,E, AU - Edery,P, AU - Farra,C, AU - Gerard,M, AU - Héron,D, AU - Leheup,B, AU - Le Merrer,M, AU - Lyonnet,S, AU - Martin-Coignard,D, AU - Mathieu,M, AU - Thauvin-Robinet,C, AU - Verloes,A, AU - Colleaux,L, AU - Munnich,A, AU - Cormier-Daire,V, Y1 - 2009/07/29/ PY - 2009/8/1/entrez PY - 2009/8/1/pubmed PY - 2011/3/3/medline SP - 797 EP - 802 JF - Journal of medical genetics JO - J. Med. Genet. VL - 47 IS - 12 N2 - Microcephalic osteodysplastic primordial dwarfism type II (MOPD II, MIM 210720) and Seckel syndrome (SCKL, MIM 210600) belong to the primordial dwarfism group characterised by intrauterine growth retardation, severe proportionate short stature, and pronounced microcephaly. MOPD II is distinct from SCKL by more severe growth retardation, radiological abnormalities, and absent or mild mental retardation. Seckel syndrome is associated with defective ATR dependent DNA damage signalling. In 2008, loss-of-function mutations in the pericentrin gene (PCNT) have been identified in 28 patients, including 3 SCKL and 25 MOPDII cases. This gene encodes a centrosomal protein which plays a key role in the organisation of mitotic spindles. The aim of this study was to analyse PCNT in a large series of SCKL-MOPD II cases to further define the clinical spectrum associated with PCNT mutations. Among 18 consanguineous families (13 SCKL and 5 MOPDII) and 6 isolated cases (3 SCKL and 3 MOPD II), 13 distinct mutations were identified in 5/16 SCKL and 8/8 MOPDII including five stop mutations, five frameshift mutations, two splice site mutations, and one apparent missense mutation affecting the last base of exon 19. Moreover, we demonstrated that this latter mutation leads to an abnormal splicing with a predicted premature termination of translation. The clinical analysis of the 5 SCKL cases with PCNT mutations showed that they all presented minor skeletal changes and clinical features compatible with MOPDII diagnosis. It is therefore concluded that, despite variable severity, MOPDII is a genetically homogeneous condition due to loss-of-function of pericentrin. SN - 1468-6244 UR - https://www.unboundmedicine.com/medline/citation/19643772/Molecular_analysis_of_pericentrin_gene__PCNT__in_a_series_of_24_Seckel/microcephalic_osteodysplastic_primordial_dwarfism_type_II__MOPD_II__families_ L2 - http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=19643772 DB - PRIME DP - Unbound Medicine ER -