PMC9868407_01
Clinical characteristics of eye, finger length, and hand joint. (A) Slit lamp examination after pupil dilatation completely reveals the equatorial region of the lens as well as bilateral microspherophakia. (B) PENTACAM shows that the lens of the proband is thicker than that of the emmetropic child in same age (control), red line: Thickness; the equatorial diameter was smaller, blue line: Actual equatorial diameter measurement of the patient's lens and the presumed value in the control eye; green line: Measurable value in the control eye. (C) UBM shows the wide angle of the anterior chamber in the proband and emmetropic child (control) (upper, right eye); the curvature of the anterior lens capsule increased and bulged forward compared to the control (lower, right eye). (D) Middle finger length measurement indicates brachydactyly (5.1 cm, -2.4 standard deviation); the right hand of the proband (at age eight, arrows) show brachydactyly and the absence of hand joint stiffness (make a full fist) comparing to a control of the same age and sex. (E) The proband's lens was thicker and thickened with age between 8 and 11 years of age, compared with emmetropic children (control) and measurements reported in the literature.
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F1
Slit lamp tests revealed bilateral microspherophakia and showed that the equatorial region of the lens was fully visible after pupil dilation (Figure 1A). PENTACAM illustrated visually that the lens of the proband was thicker than normal children (control) of the same age (Figure 1B, red line). Although it was difficult for PENTACAM to measure in vivo the equatorial diameter of the lens in normal subject after adequate pupil dilatation, the patient's lens equatorial diameter (right 7.33 mm and left 7.17 mm) was seen to be smaller than that of normal control child (Figure 1B, blue line, presumed value 9.62 mm) and smaller than that of lenses at the same age measured ex vivo. Ultrasound biomicroscopy demonstrated a wide angle of the anterior chamber, the iris and ciliary body showed no obvious abnormalities, the curvature of the anterior lens capsule increased and bulged forward, and the gap between the lens equatorial region of the lens and ciliary body became larger (Figure 1C). Moreover, the patient exhibited brachydactyly (5.1 cm, -2.4 SD) but did not report hand joint stiffness (Figure 1D, arrows) and was not of short stature at 8 years old (height 124 cm, -1.6 SD).
(A) The spherical refractive error of the proband increased (more negative) from 8 to 11 years of age and was more pronounced in the left eye, with the same trend as the calculated equivalent lens power; solid line: Myopia refractive error; dashed line: equivalent lens power. (B) Pedigree with WMS4; the proband III.3 is marked with a solid square and an arrow; unaffected individuals were labeled as blank symbols. Individuals with known genotypes were labeled, and carriers were labeled with the variants (M1:c.2984G > A, M2:c.2254A > G). (C) Sanger sequencing validated the compound heterozygous ADAMTS17 variants in the WMS family. Red arrows indicate the variant sites.
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F2
It was consistent with the change in spherical refractive error (Figure 2A). Whole-exome sequencing was performed on the proband (Figure 2B; III.3, arrow) and compound heterozygous variants were successfully identified in exon 16 (c.2254A > G) and exon 21 (c.2984G > A) of ADAMTS17 (NM_139057.4). The variants of the ADAMTS17 gene were confirmed by Sanger sequencing, and co-segregation analysis of the family was performed (Figure 2C). The result suggests that these compound heterozygous ADAMTS17 variants and disease were co-segregated in this family and imply their potential role in the autosomal recessive WMS.