Abstract

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.