Microcephalic osteodysplastic primordial dwarfism type II in four Indian children with PCNT variants

Background Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II) is an autosomal recessive rare genetic condition marked by characteristic clinical symptoms of prenatal and post-natal growth retardation, reduced height, and microcephaly caused by variations in PCNT gene located on chromosome 21q22. Case presentation Four patients of Indian origin with growth deficiency and additional clinical features of MOPDII were recruited from a tertiary health care center and whole exome sequencing was performed on blood samples from these patients. Data were analyzed using standard bioinformatic algorithms and possible causal variants identified. Out of 4, 2 patients were identified to have splice site variants, one had nonsense variant, and one with single nucleotide deletion leading to frameshift in PCNT. All identified variants were in homozygous state. The variant PCNT:c.3465-1G > A has previously been reported in two unrelated patients in Israeli Druze population. The c.9273 + 1G > A variant has been documented in two independent studies, one from the United states and the other from the United Kingdom. Two mutations, a nonsense c.5299C > T and a frameshift single nucleotide deletion c.4180delG are currently mentioned in few databases only. Conclusion All four patients had significant microcephaly and growth retardation and the new variants were found to be likely pathogenic by in silico analysis. Early detection of the syndrome is essential for early interventions, proper genetic counseling and prenatal diagnosis.