Microcephalic osteodysplastic primordial dwarfism type II (MOPD II, MIM 210720) and Seckel syndrome (SCKL, MIM 210600) belong to the primordial dwarfism group characterized by intrauterine growth retardation, severe proportionate short stature and marked 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 [6, 7]. This gene encodes a centrosomal protein which plays a key role in the organization of mitotic spindles.
The aim of our study was to analyze 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), we identified thirteen distinct mutations 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. We therefore conclude that, despite variable severity, MOPDII is a genetically homogeneous condition due to loss-of function of pericentrin.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.