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E-Book 2nd Congress

  • Novel frameshift variant in the PCNT gene associated with Seckel/ Microcephalic Osteodysplastic Primordial Dwarfism Type II (SCKL/MOPDII)
  • Mahsa Mohammad Amoli,1,* Maryam Sedghi,2 Zeynab Nickhah Klashami,3 Forough Taheri,4
    1. Metabolic Disorders Research Centre, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
    2. Metabolic Disorders Research Centre, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
    3. Metabolic Disorders Research Centre, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
    4. Metabolic Disorders Research Centre, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran


  • Introduction: MOPD II (MIM 210720), as a rare autosomal recessive disorder, characterized by severe prenatal and postnatal growth retardation, microcephaly, skeletal dysplasia, severe teeth deformities, and typical facial features. The phenotype is caused by recessive loss of function mutations in the centrosomal pericentrin (PCNT; NM_006031.5) gene on chromosome 21q22.3, predominantly owning to frameshift, splice site and stop mutations. Additionally, biallelic mutations in the PCNT gene were shown to underlie some SCKL syndrome (MIM 210600) cases, while the majority of SCKL cases were occurred by mutations in ATR gene.
  • Methods: We evaluated the clinical features of a 5- year old Iranian boy with MOPDII. Subsequently, next- generation whole exome sequencing (WES) was performed to investigate genetic profile, which is followed by sanger sequencing to confirm the WES results.
  • Results: The patient presented with severe failure to thrive, short stature, microcephaly, typical craniofacial features, teeth deformity, and other suggestive characteristics of MOPD II. MOPD type II was confirmed based on a novel pathogenic true homozygous frameshift variant in the PCNT gene c.3836_3837ins17 | p. Arg1279Serfs*44, which was inherited from his healthy related- heterozygous parents.
  • Conclusion: Our investigation pinpointed a novel PCNT mutation associated with MOPD II, which is extended the mutation spectrum of the PCNT gene and improved our understanding of the molecular basis of MOPD II, especially to better perceiving the variable expressivisity. Moreover, establishing the correct diagnosis in an individual with MOPD II is therefore essential for adequate preventive disease management and determining high risk indices for cerebral vessel insults, cardiomyopathy and early onset type 2 diabetes.
  • Keywords: MOPD II, PCNT gene, growth retardation, microcephaly, novel frameshift mutation