PMC8546181_01
(A,A1) are the imaging examination results of the patient 1 ((A): the echo intensity of the skull is obviously weaker than the midline of the brain, (A1): Micromelia, leg posture is fixed and twisted), (B,B1) are the imaging examination results of patient 2 [(B): short and curved femur and humerus,(B1): spine had "beaded changes"] (C) is the imaging examination results of patient 3 (tetraphocomelia, abnormal posturing, decreased calvarial and long bones ossification, thin ribs), (D) is the imaging examination results of patient 4, [(D): Decreased skull echogenicity. (D1): pneumonia,bell-shaped thorax and some of the ribs are rachitic rosary], (E-E2) are the teeth imaging examination results and the appearance of patient 5.
fgene-12-732621-g001.jpg
PMC8546181_02_fgene-12-732621-g001.jpg
F1
Medical imaging examination showed carious teeth, alveolar bone loss around teeth, shortened dental roots, taurodontia and abnormality of the mandible (Figures 1E-E2).
The family tree and sanger sequencing results.
fgene-12-732621-g002.jpg
PMC8546181_02_fgene-12-732621-g002.jpg
F2
Medical imaging examination showed carious teeth, alveolar bone loss around teeth, shortened dental roots, taurodontia and abnormality of the mandible (Figures 1E-E2). Genealogy and sequencing results are shown in Figure 2.
(A), Conservative analysis of the variations; (B-E) Three-dimensional structures of alkaline phosphatase [(B): wild-type, (C): c.1247G > T/p.Gly416Val mutant-type, (D): c.707A > G/p.Tyr236Cys mutant-type, c.1178A > G/p.Asn393Ser mutant-type]; (F), in silico predictions. The impact of both of the ALPL variants was predicted using five in silico tools.
fgene-12-732621-g003.jpg
PMC8546181_02_fgene-12-732621-g003.jpg
F3
CLUSTAL W was used for conservative analysis of three variations (Figure 3A). Taster, and CADD (Figure 3F). Predictive software suggested that c.1247G > T/p.Gly416Val and c.707A > G/p.Tyr236Cys were harmful variations, while for c.1178A > G/p.Asn393Ser, only Mutation Taster and CADD supported the possibility that this variation was harmful. The c.1247G > T/p.Gly416Val was assessed to be likely pathogenic (PM1, PM2, PM3, PP3, and PP4), c.707A > G/p.Tyr236Cys was assessed to be likely pathogenic (PM1, PM2, PM3, PP3, and PP4) and c.1178A > G/p.Asn393Ser was assessed to be likely pathogenic (PM1, PM2, PM3, PM5, and PP4) by the ACMG/AMP guidelines.
PMC8546181_02
(A,A1) are the imaging examination results of the patient 1 ((A): the echo intensity of the skull is obviously weaker than the midline of the brain, (A1): Micromelia, leg posture is fixed and twisted), (B,B1) are the imaging examination results of patient 2 [(B): short and curved femur and humerus,(B1): spine had "beaded changes"] (C) is the imaging examination results of patient 3 (tetraphocomelia, abnormal posturing, decreased calvarial and long bones ossification, thin ribs), (D) is the imaging examination results of patient 4, [(D): Decreased skull echogenicity. (D1): pneumonia,bell-shaped thorax and some of the ribs are rachitic rosary], (E-E2) are the teeth imaging examination results and the appearance of patient 5.
fgene-12-732621-g001.jpg
PMC8546181_02_fgene-12-732621-g001.jpg
F1
Medical imaging examination showed carious teeth, alveolar bone loss around teeth, shortened dental roots, taurodontia and abnormality of the mandible (Figures 1E-E2).
The family tree and sanger sequencing results.
fgene-12-732621-g002.jpg
PMC8546181_02_fgene-12-732621-g002.jpg
F2
Medical imaging examination showed carious teeth, alveolar bone loss around teeth, shortened dental roots, taurodontia and abnormality of the mandible (Figures 1E-E2). Genealogy and sequencing results are shown in Figure 2.
(A), Conservative analysis of the variations; (B-E) Three-dimensional structures of alkaline phosphatase [(B): wild-type, (C): c.1247G > T/p.Gly416Val mutant-type, (D): c.707A > G/p.Tyr236Cys mutant-type, c.1178A > G/p.Asn393Ser mutant-type]; (F), in silico predictions. The impact of both of the ALPL variants was predicted using five in silico tools.
fgene-12-732621-g003.jpg
PMC8546181_02_fgene-12-732621-g003.jpg
F3
CLUSTAL W was used for conservative analysis of three variations (Figure 3A). Taster, and CADD (Figure 3F). Predictive software suggested that c.1247G > T/p.Gly416Val and c.707A > G/p.Tyr236Cys were harmful variations, while for c.1178A > G/p.Asn393Ser, only Mutation Taster and CADD supported the possibility that this variation was harmful. The c.1247G > T/p.Gly416Val was assessed to be likely pathogenic (PM1, PM2, PM3, PP3, and PP4), c.707A > G/p.Tyr236Cys was assessed to be likely pathogenic (PM1, PM2, PM3, PP3, and PP4) and c.1178A > G/p.Asn393Ser was assessed to be likely pathogenic (PM1, PM2, PM3, PM5, and PP4) by the ACMG/AMP guidelines.