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Case Reports
. 2021 Sep;9(9):e1761.
doi: 10.1002/mgg3.1761. Epub 2021 Jul 31.

A novel homozygous mutation of the PCNT gene in a Chinese patient with microcephalic osteodysplastic primordial dwarfism type II

Haifeng Liu  1 , Na Tao  2 , Yan Wang  1 , Yang Yang  2 , Xiaoli He  1 , Yu Zhang  1 , Yuantao Zhou  1 , Xiaoning Liu  3 , Xingxing Feng  4 , Meiyuan Sun  2 , Fang Xu  2 , Yanfang Su  2 , Li Li  1
Affiliations
Case Reports

A novel homozygous mutation of the PCNT gene in a Chinese patient with microcephalic osteodysplastic primordial dwarfism type II

Haifeng Liu et al. Mol Genet Genomic Med. 2021 Sep.

Abstract

Background: Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare autosomal recessive disorder characterized by severe pre- and postnatal growth restrictions, microcephaly, skeletal dysplasia, severe teeth deformities, and typical facial features. Previous studies have shown that MOPD II is associated with mutations in the pericentrin (PCNT) gene.

Methods: We evaluated the clinical features of a 10-year and 7-month-old Chinese girl with MOPD II. Subsequently, next-generation sequencing and flow cytometry were performed to investigate genetic characteristics and the expression of PCNT protein respectively.

Results: The patient presented with short stature, microcephaly, typical craniofacial features, teeth deformity, thrombocytosis, and a delayed bone age (approximately 7 years). No abnormality in growth hormone or insulin-like growth factor 1 was detected. Notably, the patient was found to carry a novel homozygous PCNT mutation (c.6157G>T, p.Glu2053Ter), which was inherited from her healthy heterozygous parents. Meanwhile, significant deficiency of PCNT expression was identified in the patient.

Conclusion: Our study identified a novel PCNT mutation associated with MOPD II, expanded the mutation spectrum of the PCNT gene and improved our understanding of the molecular basis of MOPD II.

Keywords: MOPD II; PCNT gene; growth restriction; microcephaly; novel homozygous mutation.

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Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this manuscript.

Figures

FIGURE 1
FIGURE 1
Clinical characteristics of the patient. (a) The patient showed significant craniofacial features, including microcephaly, sparse hair, prominent eyes, broad nasal bridge and root, full nose tip, as well as proportionally small ears. (b) Small and malformed teeth with wide interdental spacing were observed in the patient. (c) The patient had a short stature but no skin pigmentation, coxa vara, or talipes equinovarus
FIGURE 2
FIGURE 2
Imaging findings of the patient. (a) Bone age of the patient was examined through left hand and wrist X‐ray. Ossification centers of the left carpus and ulna were apparent (the number of ossification centers of the carpus was nine), and the medial sesamoid of the thumb was not observed. (b) Hypophysis MRI showed no obvious abnormalities. (c) Brain CT revealed no definite pathological signs. CT, computed tomography; MRI, magnetic resonance imaging
FIGURE 3
FIGURE 3
Mutational analysis of all subjects. (a) The patient (II‐1) was found to have a novel homozygous PCNT mutation (c.6157G>T, p.Glu2053Ter), which was inherited from her healthy heterozygous parents (father, I‐1; mother, I‐2). Nucleotide 6157 in the coding region was changed from guanine (G) to thymine (T) (c.6157G>T), which altered the glutamate to a premature termination codon at the site of 2053 (p.Glu2053Ter). Mutation sites are indicated by red arrows and squares. (b) Pedigree of the family. The father (I‐1) and mother (I‐2) were consanguineous. They were confirmed to be healthy carriers of this mutation without any symptoms, while their daughter (II‐1) carrying the homozygous PCNT mutation showed typical symptoms of MOPD II
FIGURE 4
FIGURE 4
The expressions of PCNT protein in PBMCs isolated from the patient and her parents. In the patient, the peak for PCNT‐positive cells nearly overlapped with the blank control peak. The percentage of PCNT‐positive cells was 0.82%. In her parents, the peaks for PCNT‐positive cells partially shifted to right compared with the blank control peak and the percentages of PCNT‐positive cells were 46.3% (in the father) and 42.0% (in the mother), respectively. The peaks of the blank control and the subjects are marked in red and blue, respectively. PBMCs, peripheral blood mononuclear cells
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