PMC9492974_01
Head and facial features of the child at the age of 1 year. (A) Wide eye spacing, sparse eyebrows, light color; (B) Loose hair, sparse hair, light color; (C) abnormal auricle appearance; (D) dry and eczema-prone skin.
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F1
As shown in Figure 1, she exhibited some unique head and facial features, including prominent forehead, white skin, yellowish hair color, slightly wider eye distance, scant eyebrows, light complexion, bilateral auricle shape abnormity, Both pupils are equal in size and round, and dry skin that was prone to eczema (Figure 1).
Comparison of the results of two cardiac ultrasonographies of the child (A) ventricular septal defect and pseudomonal tumor formation (rupture of about 2.5 mm and 1.8 mm) were found in July 2020; (B) Ventricular septal defect and pseudo membrane tumor formation (1.3 mm rupture) were found by heart color doppler ultrasound in January 2021.
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F2
Cardiac ultrasonography in January 2021 revealed ventricular septal defect and pseudo membrane neoplasm (1.3 mm rupture) (Figure 2B).
Radiographs of the child's hip joint show slightly flat and shallow bilateral acetabular fossa and enlarged bilateral acetabular angle.
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F3
Radiography of the hip joint showed bilateral hip dysplasia (Figure 3).
PMC9492974_02
Comparison of the results of two cardiac ultrasonographies of the child (A) ventricular septal defect and pseudomonal tumor formation (rupture of about 2.5 mm and 1.8 mm) were found in July 2020; (B) Ventricular septal defect and pseudo membrane tumor formation (1.3 mm rupture) were found by heart color doppler ultrasound in January 2021.
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F2
Cardiac ultrasonography in January 2021 revealed ventricular septal defect and pseudo membrane neoplasm (1.3 mm rupture) (Figure 2B).
(A) Children with family figure for NSLH2 clinical phenotype. Her father (I-a) and mother (I-b) had normal clinical manifestations; (B) children with children and parents Sanger sequencing diagram (II-a) for c. 371 A>G heterozygous mutations. Her father (I-a) and mother (I-b) the site are for the wild type.
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F4
The patient had a novel heterozygous mutation in exon 3 of the coding region of PPP1CB (CHR2-29001861), and the nucleotide 371 changed from A to G (C. 371A   G) (Figure 4A), resulting in the mutation of the amino acid at the 124th position from histidine to arginine (p.H124R). Sanger sequencing verified that the child's parents did not carry the mutation at the site, which was a spontaneous mutation (Figure 4B), according to the ACMG guidelines.
Conservation and 3D molecular model of PPP1CB mutations. (A) Protein alignment showing PPP1CB p.H124 occurred at evolutionarily conserved amino acids (in red box) across 11 genera; (B) Wild type of PPP1CB; (C) Three-dimensional molecular models of wild-type protein at site p.H124; (D) Abnormal structure of mutant-type protein.
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F5
The alignment of PPP1CB from different genera namely Homo, Pan, Macaca, Canis, Bos, Mus, Rattus, Gallus, Danio, Drosophila, and Anopheles is shown in Figure 5A. The three-dimensional structures of wild-type PPP1CB was simulated according to the crystal structure (Figure 5B). In this respect, our prediction study revealed that the novel mutation possibly lead to protein dysfunction (Figures 5C,D).