PMC10414535_01
Brain MRI of patient 1 at 2 years of age (A, B) in sagittal T1-weighted and axial T2-weighted images subsequently demonstrates prominent extra-axial spaces of both cerebral hemispheres along with moderate cerebellar and vermian atrophy, ex vacuo dilatation of the fourth ventricle, and enlargement of the retro-cerebellar fossa. In addition, there is a vertical orientation of the posterior corpus callosum. Similar findings are also demonstrated in patient 2 at 18 months of age [(C,D) sagittal T1-weighted and axial T2-weighted images], along with a thin corpus callosum. FLAIR weighted images, not included, did not depict any abnormal signal in the brain parenchyma.
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F1
The FLAIR weighted images did not demonstrate any abnormal signal in the supratentorial and/or infratentorial regions (Figure 1) (Figure 1A, sagittal T1-weighted image, and Figure 1B, T2-weighted image) Figure 1B. In addition, thinning of the corpus callosum and cerebellar atrophy with enlarged retro-cerebellar fossa were present (Figure 1) (Figure 1C, sagittal T1-weighted image, and Figure 1D, T2-weighted image).
CT of the abdomen for patient 2. Coronal images of the CT scan of the abdomen in renal and excretory phases (A,B) demonstrating multiple hypodensities in both kidneys consistent with the medullary cystic disease complex.
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F2
The FLAIR weighted images did not demonstrate any abnormal signal in the supratentorial and/or infratentorial regions (Figure 1) (Figure 1A, sagittal T1-weighted image, and Figure 1B, T2-weighted image) Figure 1B. In addition, thinning of the corpus callosum and cerebellar atrophy with enlarged retro-cerebellar fossa were present (Figure 1) (Figure 1C, sagittal T1-weighted image, and Figure 1D, T2-weighted image). CT scan of the abdomen findings was consistent with medullary cystic disease complex (Figure 2).
(A) Family pedigree and segregation analysis of the c.1049_1051delCAG (p.Ala350del variant (+) in the affected siblings and family members. The proband is indicated by the arrow. (B) Representative chromatogram showing the variant in a homozygous state in the affected, heterozygous (carrier) state in the parents, and wild-type state in a healthy control. The deleted bases are indicated inside a box in the normal chromatogram.
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F3
S1). Though this region harbored other potential candidate genes associated with conditions overlapping with the patients' phenotypes, no variants were identified in any of those genes. Sanger sequencing confirmed the presence of the variant in the corresponding allelic state in both the patients and their parents (Figure 3B). The segregation of the variant is presented in Figure 3A.