Microcephalic osteodysplastic primordial dwarfism type II: Additional nine patients with implications on phenotype and genotype correlation.
Adolescent
Antigens
/ genetics
Child
Child, Preschool
Consanguinity
Dwarfism
/ complications
Egypt
/ epidemiology
Female
Fetal Growth Retardation
/ epidemiology
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
Infant
Male
Microcephaly
/ complications
Mutation
Osteochondrodysplasias
/ complications
Phenotype
Siblings
PCNT
MOPD II
microcephalic osteodysplastic primordial dwarfism
orodental anomalies
rootless teeth
tooth agenesis
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
09
07
2019
revised:
20
02
2020
accepted:
09
03
2020
pubmed:
9
4
2020
medline:
29
1
2021
entrez:
9
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32267100
doi: 10.1002/ajmg.a.61585
doi:
Substances chimiques
Antigens
0
pericentrin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1407-1420Informations de copyright
© 2020 Wiley Periodicals, Inc.
Références
Alkuraya, F. S. (2015). Primordial dwarfism. Current Opinion in Endocrinology & Diabetes and Obesity, 22(1), 55-64. https://doi.org/10.1097/med.0000000000000121
Aoyama, K. I., Kimura, M., Yamazaki, H., Uchibori, M., Kojima, R., Osawa, Y., … Nishimura, G. (2019). New PCNT candidate missense variant in a patient with oral and maxillofacial osteodysplasia: A case report. BMC Medical Genetics, 20(1), 126.
Bober, M. B., & Jackson, A. P. (2017). Microcephalic Osteodysplastic primordial dwarfism, type II: A clinical review. Current Osteoporosis Reports, 15(2), 61-69. https://doi.org/10.1007/s11914-017-0348-1
Griffith, E., Walker, S., Martin, C.-A., Vagnarelli, P., Stiff, T., Vernay, B., … O'Driscoll, M. (2008). Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling. Nature Genetics, 40(2), 232-236. https://doi.org/10.1038/ng.2007.80
Hall, J. G. (2013). The smallest of the small. Gene, 528(1), 55-57. https://doi.org/10.1016/j.gene.2013.03.081
Hall, J. G., Flora, C., Scott, C. I., Pauli, R. M., & Tanaka, K. I. (2004). Majewski osteodysplastic primordial dwarfism type II (MOPD II): Natural history and clinical findings. American Journal of Medical Genetics, 130A(1), 55-72. https://doi.org/10.1002/ajmg.a.30203
Kantaputra, P. N. (2002). Apparently new osteodysplastic and primordial short stature with severe microdontia, opalescent teeth, and rootless molars in two siblings. American Journal of Medical Genetics, 111(4), 420-428. https://doi.org/10.1002/ajmg.10589
Kantaputra, P. N., Tanpaiboon, P., Unachak, K., & Praphanphoj, V. (2004). Microcephalic osteodysplastic primordial dwarfism with severe microdontia and skin anomalies: Confirmation of a new syndrome. American Journal of Medical Genetics, 130A(2), 181-190. https://doi.org/10.1002/ajmg.a.30079
Kantaputra, P., Tanpaiboon, P., Porntaveetus, T., Ohazama, A., Sharpe, P., Rauch, A., … Thiel, C. T. (2011). The smallest teeth in the world are caused by mutations in the PCNT gene. American Journal of Medical Genetics, Part A, 155(6), 1398-1403. https://doi.org/10.1002/ajmg.a.33984
Li, F. F., Wang, X. D., Zhu, M. W., Lou, Z. H., Zhang, Q., Zhu, C.Y., Feng, H. L., Lin, Z. G., Liu, S. L. (2015). Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type ll associated with multiple intracranial aneurysms. Metabolic Brain Disease, 30(6), 1387-1394. https://doi.org/10.1007/s11011-015-9712-y
Lorenzo-Betancor, O., Blackburn, P. R., Edwards, E., Vázquez-do-Campo, R., Klee, E. W., Labbé, C., … Ross, O. A. (2018). PCNT point mutations and familial intracranial aneurysms. Neurology, 91(23), e2170-e2181. https://doi.org/10.1212/WNL.0000000000006614
Pachajoa, H., Ruiz-Botero, F., Isaza, C. (2014). A new mutation of the PCNT gene in a Colombian patient with microcephalic osteodysplastic primordial dwarfism type II: a case report. Journal of Medical Case Reports, 13(8), 191. hhtps://doi.org/10.1186/1752-1947-8-191
Rauch, A., Thiel, C. T., Schindler, D., Wick, U., Crow, Y. J., Ekici, A. B., … Reis, A. (2008). Mutations in the Pericentrin (PCNT) gene cause primordial dwarfism. Science, 319(5864), 816-819. https://doi.org/10.1126/science.1151174
Rauch, A. (2011). The shortest of the short: Pericentrin mutations and beyond. Best Practice & Research. Clinical Endocrinology & Metabolism, 25(1), 125-130. https://doi.org/10.1016/j.beem.2010.10.015
Shaheen, R., Maddirevula, S., Ewida, N., Alsahli, S., Abdel-Salam, G. M. H., Zaki, M. S., … Alkuraya, F. S. (2019). Genomic and phenotypic delineation of congenital microcephaly. Genetics in Medicine, 21(3), 545-552. https://doi.org/10.1038/s41436-018-0140-3
Weiss, K., Ekhilevitch, N., Cohen, L., Bratman-Morag, S., Bello, R., Martinez, A. F., … Muenke, M. (2019). Identification of a novel PCNT founder pathogenic variant in the Israeli Druze population. European Journal of Medical Genetics., 63, 103643. https://doi.org/10.1016/j.ejmg.2019.03.007
Willems, M., Geneviève, D., Borck, G., Baumann, C., Baujat, G., Bieth, E., … Cormier-Daire, V. (2010). Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. Journal of Medical Genetics, 47(12), 797-802. https://doi.org/10.1136/jmg.2009.067298