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Identification of three novel mutations in PCNT in vietnamese patients with microcephalic osteodysplastic primordial dwarfism type II.
Genes Genomics. 2021 02; 43(2):115-121.GG

Abstract

BACKGROUND

Primordial dwarfism (PD) is a group of genetically heterogeneous disorders related to developmental disabilities occurring in the uterus and prolongs during all stages of life, resulting in short stature, facial deformities and abnormal brain.

OBJECTIVE

To determine the exact cause of the disease in two Vietnamese patients priory diagnosed with PD by severe pre-and postnatal growth retardation with marked microcephaly and some bone abnormalities.

METHODS

Whole-exome sequencing was performed for the two patients and mutations in genes related to PD were screened. Sanger sequencing was applied to examine the mutations in the patients of their families.

RESULTS

Three novel mutations in the PCNT gene which have not been reported previously were identified in the two patients. Of which, two frameshift mutations (p.Thr479Profs*6 and p.Glu2742Alafs*8) were detected in patient I and one stop-gained mutation (p.Gln1907*) was detected in the patient II. These mutations may result in a truncated PCNT protein, leading to an inactivated PACT domain corresponding to residue His3138-Trp3216 of PCNT protein. Therefore, the three mutations may cause a deficiency of protein functional activity and result in the phenotypes of primordial dwarfism in the two patients.

CONCLUSIONS

Clinical presentations in combination with genetic analyses supported an accurate diagnosis of the two patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II). In addition, these results have important implications for prenatal genetic screening and genetic counseling for the families.

Authors+Show Affiliations

Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam. Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam.Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam.Department of Medical Genetics, Metabolism and Endocrinology, Vietnam National Children's Hospital, 18/879 La Thanh, Dong Da, Hanoi, 100000, Vietnam.Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam.Department of Medical Genetics, Metabolism and Endocrinology, Vietnam National Children's Hospital, 18/879 La Thanh, Dong Da, Hanoi, 100000, Vietnam.Institute of Genome Research, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam. nhhoang@igr.ac.vn. Graduate University of Sciences and Technology, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam. nhhoang@igr.ac.vn.

Pub Type(s)

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

Language

eng

PubMed ID

33460028

Citation

Nguyen, Thu Hien, et al. "Identification of Three Novel Mutations in PCNT in Vietnamese Patients With Microcephalic Osteodysplastic Primordial Dwarfism Type II." Genes & Genomics, vol. 43, no. 2, 2021, pp. 115-121.
Nguyen TH, Nguyen NL, Vu CD, et al. Identification of three novel mutations in PCNT in vietnamese patients with microcephalic osteodysplastic primordial dwarfism type II. Genes Genomics. 2021;43(2):115-121.
Nguyen, T. H., Nguyen, N. L., Vu, C. D., Ngoc, C. T. B., Nguyen, N. K., & Nguyen, H. H. (2021). Identification of three novel mutations in PCNT in vietnamese patients with microcephalic osteodysplastic primordial dwarfism type II. Genes & Genomics, 43(2), 115-121. https://doi.org/10.1007/s13258-020-01032-5
Nguyen TH, et al. Identification of Three Novel Mutations in PCNT in Vietnamese Patients With Microcephalic Osteodysplastic Primordial Dwarfism Type II. Genes Genomics. 2021;43(2):115-121. PubMed PMID: 33460028.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of three novel mutations in PCNT in vietnamese patients with microcephalic osteodysplastic primordial dwarfism type II. AU - Nguyen,Thu Hien, AU - Nguyen,Ngoc-Lan, AU - Vu,Chi Dung, AU - Ngoc,Can Thi Bich, AU - Nguyen,Ngoc Khanh, AU - Nguyen,Huy Hoang, Y1 - 2021/01/18/ PY - 2020/09/01/received PY - 2020/12/19/accepted PY - 2021/1/19/pubmed PY - 2021/12/18/medline PY - 2021/1/18/entrez KW - MOPD II KW - Microcephaly KW - PCNT gene KW - Primordial dwarfism SP - 115 EP - 121 JF - Genes & genomics JO - Genes Genomics VL - 43 IS - 2 N2 - BACKGROUND: Primordial dwarfism (PD) is a group of genetically heterogeneous disorders related to developmental disabilities occurring in the uterus and prolongs during all stages of life, resulting in short stature, facial deformities and abnormal brain. OBJECTIVE: To determine the exact cause of the disease in two Vietnamese patients priory diagnosed with PD by severe pre-and postnatal growth retardation with marked microcephaly and some bone abnormalities. METHODS: Whole-exome sequencing was performed for the two patients and mutations in genes related to PD were screened. Sanger sequencing was applied to examine the mutations in the patients of their families. RESULTS: Three novel mutations in the PCNT gene which have not been reported previously were identified in the two patients. Of which, two frameshift mutations (p.Thr479Profs*6 and p.Glu2742Alafs*8) were detected in patient I and one stop-gained mutation (p.Gln1907*) was detected in the patient II. These mutations may result in a truncated PCNT protein, leading to an inactivated PACT domain corresponding to residue His3138-Trp3216 of PCNT protein. Therefore, the three mutations may cause a deficiency of protein functional activity and result in the phenotypes of primordial dwarfism in the two patients. CONCLUSIONS: Clinical presentations in combination with genetic analyses supported an accurate diagnosis of the two patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II). In addition, these results have important implications for prenatal genetic screening and genetic counseling for the families. SN - 2092-9293 UR - https://www.unboundmedicine.com/medline/citation/33460028/Identification_of_three_novel_mutations_in_PCNT_in_vietnamese_patients_with_microcephalic_osteodysplastic_primordial_dwarfism_type_II_ L2 - https://scite.ai/reports/33460028 DB - PRIME DP - Unbound Medicine ER -