Novel CENPJ mutation causes Seckel syndrome
- 1Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- 2Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
- 3Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- 4Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia
- 5Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- Correspondence to Fowzan S Alkuraya, Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, MBC 03, PO Box 3354, Riyadh 11211, Saudi Arabia;
- Received 31 December 2009
- Revised 3 March 2010
- Accepted 5 March 2010
Background Primordial dwarfism (PD) is an extremely rare, clinicallyheterogeneous condition characterised by profound prenatal and postnatal growth restriction among other manifestations that are helpful in the clinical classification. Recently, mutation of PCNT was reported in the context of two overlapping forms of PD: Seckel syndrome and Majewskiosteodysplastic primordial dwarfism type II (MOPDII).
Aim To clinically and molecularly characterise a consanguineous family with Seckel syndrome.
Methods Clinical evaluation, linkage analysis, homozygosity mapping and mutation analysis.
Results Unexpectedly, linkage analysis led to the identification of a novel splice-site mutation in CENPJ that segregates with the phenotype in this family.
Conclusion This report establishes for the first time that mutation of CENPJ can lead to Seckel syndrome and calls for further investigation of the role played by other microcephaly related genes in the pathogenesis of PD.
MSA-D and RS contributed equally to this work.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the KFSHRC IRB #208006.
Provenance and peer review Not commissioned; externally peer reviewed.