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Identification of three novel mutations in PCNT in vietnamese patients with microcephalic osteodysplastic primordial dwarfism type II

Genes & Genomics 2021년 43권 2호 p.115 ~ 121
Nguyen Thu Hien, Nguyen Ngoc-Lan, Vu Chi Dung, Ngoc Can Thi Bich, Nguyen Ngoc Khanh, Nguyen Huy Hoang,
소속 상세정보
 ( Nguyen Thu Hien ) - Vietnam Academy of Science and Technology Institute of Genome Research
 ( Nguyen Ngoc-Lan ) - Vietnam Academy of Science and Technology Institute of Genome Research
 ( Vu Chi Dung ) - Vietnam National Children’s Hospital Department of Medical Genetics, Metabolism and Endocrinology
 ( Ngoc Can Thi Bich ) - Vietnam Academy of Science and Technology Institute of Genome Research
 ( Nguyen Ngoc Khanh ) - Vietnam National Children’s Hospital Department of Medical Genetics, Metabolism and Endocrinology
 ( Nguyen Huy Hoang ) - Vietnam Academy of Science and Technology Institute of Genome Research

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.

키워드

Microcephaly; MOPD II; PCNT gene; Primordial dwarfism

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