Microcephalic osteodysplastic primordial dwarfism type II in four Indian children with PCNT variants
Abstract 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 locate...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-01-01
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| Series: | Egyptian Journal of Medical Human Genetics |
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| Online Access: | https://doi.org/10.1186/s43042-025-00636-4 |
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| author | Amit Singh Mahak Garg Mohammed Shariq Preeti Khetarpal Inusha Panigrahi |
| author_facet | Amit Singh Mahak Garg Mohammed Shariq Preeti Khetarpal Inusha Panigrahi |
| author_sort | Amit Singh |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-35d9e8967de7402da71814567b0d09c2 |
| institution | Kabale University |
| issn | 2090-2441 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj-art-35d9e8967de7402da71814567b0d09c22025-01-19T12:25:57ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412025-01-012611710.1186/s43042-025-00636-4Microcephalic osteodysplastic primordial dwarfism type II in four Indian children with PCNT variantsAmit Singh0Mahak Garg1Mohammed Shariq2Preeti Khetarpal3Inusha Panigrahi4Laboratory for Reproductive and Developmental Disorders, Department of Human Genetics and Molecular Medicine, Central University of PunjabGenetic Metabolic Unit, Department of Pediatrics, PGIMERGenetic Metabolic Unit, Department of Pediatrics, PGIMERLaboratory for Reproductive and Developmental Disorders, Department of Human Genetics and Molecular Medicine, Central University of PunjabGenetic Metabolic Unit, Department of Pediatrics, PGIMERAbstract 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.https://doi.org/10.1186/s43042-025-00636-4Autosomal recessiveFailure to thriveMicrocephalyPCNTMOPD II |
| spellingShingle | Amit Singh Mahak Garg Mohammed Shariq Preeti Khetarpal Inusha Panigrahi Microcephalic osteodysplastic primordial dwarfism type II in four Indian children with PCNT variants Egyptian Journal of Medical Human Genetics Autosomal recessive Failure to thrive Microcephaly PCNT MOPD II |
| title | Microcephalic osteodysplastic primordial dwarfism type II in four Indian children with PCNT variants |
| title_full | Microcephalic osteodysplastic primordial dwarfism type II in four Indian children with PCNT variants |
| title_fullStr | Microcephalic osteodysplastic primordial dwarfism type II in four Indian children with PCNT variants |
| title_full_unstemmed | Microcephalic osteodysplastic primordial dwarfism type II in four Indian children with PCNT variants |
| title_short | Microcephalic osteodysplastic primordial dwarfism type II in four Indian children with PCNT variants |
| title_sort | microcephalic osteodysplastic primordial dwarfism type ii in four indian children with pcnt variants |
| topic | Autosomal recessive Failure to thrive Microcephaly PCNT MOPD II |
| url | https://doi.org/10.1186/s43042-025-00636-4 |
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