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Microcephalic osteodysplastic primordial dwarfism type II: Additional nine patients with implications on phenotype and genotype correlation.
Am J Med Genet A. 2020 06; 182(6):1407-1420.AJ

Abstract

PCNT encodes a large coiled- protein localizing to pericentriolar material and is associated with microcephalic osteodysplastic primordial dwarfism type II syndrome (MOPD II). We report our experience of nine new patients from seven unrelated consanguineous Egyptian families with the distinctive clinical features of MOPD II in whom a customized NGS panel showed homozygous truncating variants of PCNT. The NGS panel results were validated thereafter using Sanger sequencing revealing three previously reported and three novel PCNT pathogenic variants. The core phenotype appeared homogeneous to what had been reported before although patients differed in the severity showing inter and intra familial variability. The orodental pattern showed atrophic alveolar ridge (five patients), rootless tooth (four patients), tooth agenesis (three patients), and malformed tooth (three patients). In addition, mesiodens was a novel finding found in one patient. The novel c.9394-1G>T variant was found in two sibs who had tooth agenesis. CNS anomalies with possible vascular sequelae were documented in two male patients (22.2%). Simplified gyral pattern with poor development of the frontal horns of lateral ventricles was seen in four patients and mild thinning of the corpus callosum in two patients. Unilateral coronal craniosynstosis was noted in one patient and thick but short corpus callosum was an unusual finding noted in another. The later has not been reported before. Our results refine the clinical, neuroradiological, and orodental features and expand the molecular spectrum of MOPD II.

Authors+Show Affiliations

Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt. Orodental Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt. Medical Molecular Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt. Orodental Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt. Medical Molecular Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt. Human Cytogenetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt.Centre of Excellence for Human Genetics, National Research Centre, Cairo, Egypt. Medical Molecular Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32267100

Citation

Abdel-Salam, Ghada M H., et al. "Microcephalic Osteodysplastic Primordial Dwarfism Type II: Additional Nine Patients With Implications On Phenotype and Genotype Correlation." American Journal of Medical Genetics. Part A, vol. 182, no. 6, 2020, pp. 1407-1420.
Abdel-Salam GMH, Sayed ISM, Afifi HH, et al. Microcephalic osteodysplastic primordial dwarfism type II: Additional nine patients with implications on phenotype and genotype correlation. Am J Med Genet A. 2020;182(6):1407-1420.
Abdel-Salam, G. M. H., Sayed, I. S. M., Afifi, H. H., Abdel-Ghafar, S. F., Abouzaid, M. R., Ismail, S. I., Aglan, M. S., Issa, M. Y., El-Bassyouni, H. T., El-Kamah, G., Effat, L. K., Eid, M., Zaki, M. S., Temtamy, S. A., & Abdel-Hamid, M. S. (2020). Microcephalic osteodysplastic primordial dwarfism type II: Additional nine patients with implications on phenotype and genotype correlation. American Journal of Medical Genetics. Part A, 182(6), 1407-1420. https://doi.org/10.1002/ajmg.a.61585
Abdel-Salam GMH, et al. Microcephalic Osteodysplastic Primordial Dwarfism Type II: Additional Nine Patients With Implications On Phenotype and Genotype Correlation. Am J Med Genet A. 2020;182(6):1407-1420. PubMed PMID: 32267100.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microcephalic osteodysplastic primordial dwarfism type II: Additional nine patients with implications on phenotype and genotype correlation. AU - Abdel-Salam,Ghada M H, AU - Sayed,Inas S M, AU - Afifi,Hanan H, AU - Abdel-Ghafar,Sherif F, AU - Abouzaid,Maha R, AU - Ismail,Samira I, AU - Aglan,Mona S, AU - Issa,Mahmoud Y, AU - El-Bassyouni,Hala T, AU - El-Kamah,Ghada, AU - Effat,Laila K, AU - Eid,Maha, AU - Zaki,Maha S, AU - Temtamy,Samia A, AU - Abdel-Hamid,Mohamed S, Y1 - 2020/04/08/ PY - 2019/07/09/received PY - 2020/02/20/revised PY - 2020/03/09/accepted PY - 2020/4/9/pubmed PY - 2021/1/29/medline PY - 2020/4/9/entrez KW - PCNT KW - MOPD II KW - microcephalic osteodysplastic primordial dwarfism KW - orodental anomalies KW - rootless teeth KW - tooth agenesis SP - 1407 EP - 1420 JF - American journal of medical genetics. Part A JO - Am J Med Genet A VL - 182 IS - 6 N2 - PCNT encodes a large coiled- protein localizing to pericentriolar material and is associated with microcephalic osteodysplastic primordial dwarfism type II syndrome (MOPD II). We report our experience of nine new patients from seven unrelated consanguineous Egyptian families with the distinctive clinical features of MOPD II in whom a customized NGS panel showed homozygous truncating variants of PCNT. The NGS panel results were validated thereafter using Sanger sequencing revealing three previously reported and three novel PCNT pathogenic variants. The core phenotype appeared homogeneous to what had been reported before although patients differed in the severity showing inter and intra familial variability. The orodental pattern showed atrophic alveolar ridge (five patients), rootless tooth (four patients), tooth agenesis (three patients), and malformed tooth (three patients). In addition, mesiodens was a novel finding found in one patient. The novel c.9394-1G>T variant was found in two sibs who had tooth agenesis. CNS anomalies with possible vascular sequelae were documented in two male patients (22.2%). Simplified gyral pattern with poor development of the frontal horns of lateral ventricles was seen in four patients and mild thinning of the corpus callosum in two patients. Unilateral coronal craniosynstosis was noted in one patient and thick but short corpus callosum was an unusual finding noted in another. The later has not been reported before. Our results refine the clinical, neuroradiological, and orodental features and expand the molecular spectrum of MOPD II. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/32267100/Microcephalic_osteodysplastic_primordial_dwarfism_type_II:_Additional_nine_patients_with_implications_on_phenotype_and_genotype_correlation_ L2 - https://doi.org/10.1002/ajmg.a.61585 DB - PRIME DP - Unbound Medicine ER -