case_images: PMC11424399_01
case_images: Chest CT of the elder (A,B) and younger (C-E) brothers: (A) chest CT of the elder brother showing bilateral GGOs, consolidations, and reticular opacities at the age of 3 months; (B) chest CT of the elder brother showing slightly improved GGOs but aggravated consolidations at the age of 8 months; (C) chest CT of the younger brother showing GGOs, consolidations, and mediastinal lung hernia at the age of 1 month; (D) chest CT of the younger brother showing improved GGOs and consolidations at the age of 4 months; and (E) chest CT of the younger brother showing the appearance of cysts and improved GGOs and consolidations at the age of 14 months.
case_images: fped-12-1402545-g001.jpg
case_images: PMC11424399_02_fped-12-1402545-g001.jpg
case_images: F1
case_images: His chest CT was similar to his brother's, showing GGOs and consolidations, mainly distributed in the lower lungs (Figure 1C). After more than 2 months of treatment (at the age of 4 months), his chest CT improved (Figure 1D), with repeated KL-6 levels decreasing to 1,417 U/ml. After 13 months of treatment (at the age of 14 months), his chest CT showed the development of cysts and improvement in GGOs and consolidations (Figure 1E).
case_images: PMC11424399_02
case_images: Chest CT of the elder (A,B) and younger (C-E) brothers: (A) chest CT of the elder brother showing bilateral GGOs, consolidations, and reticular opacities at the age of 3 months; (B) chest CT of the elder brother showing slightly improved GGOs but aggravated consolidations at the age of 8 months; (C) chest CT of the younger brother showing GGOs, consolidations, and mediastinal lung hernia at the age of 1 month; (D) chest CT of the younger brother showing improved GGOs and consolidations at the age of 4 months; and (E) chest CT of the younger brother showing the appearance of cysts and improved GGOs and consolidations at the age of 14 months.
case_images: fped-12-1402545-g001.jpg
case_images: PMC11424399_02_fped-12-1402545-g001.jpg
case_images: F1
case_images: His chest CT was similar to his brother's, showing GGOs and consolidations, mainly distributed in the lower lungs (Figure 1C). After more than 2 months of treatment (at the age of 4 months), his chest CT improved (Figure 1D), with repeated KL-6 levels decreasing to 1,417 U/ml. After 13 months of treatment (at the age of 14 months), his chest CT showed the development of cysts and improvement in GGOs and consolidations (Figure 1E).
case_images: Brain MRI of the younger brother [(A) T1, (B) T2, (C) T2 FLAIR]: brain MRI of the younger brother revealing a widening of cerebral sulci and fissures, cortical thinning, and enlargement of the frontal and temporal angles at the age of 14 months.
case_images: fped-12-1402545-g002.jpg
case_images: PMC11424399_02_fped-12-1402545-g002.jpg
case_images: F2
case_images: His brain magnetic resonance imaging (MRI) showed a widening of cerebral sulci and fissures, cortical thinning, and enlargement of the frontal and temporal angles, without evidence of cerebral angiomatosis (Figures 2A-C).
case_images: (A,B) WES information and Sanger sequencing of NHLRC2 variants of the elder and younger brothers; (C) pedigree of the family; (D) structure of the NHLRC2 wild-type and c.1610dupT, p.L537Ffs*17 variant; and (E) novel variant (red color) and previously reported variants of NHLRC2 (black color) 1, 8-11.
case_images: fped-12-1402545-g003.jpg
case_images: PMC11424399_02_fped-12-1402545-g003.jpg
case_images: F3
case_images: The results were validated by Sanger sequencing (Figures 3A-C). The other novel variant, p.L537Ffs*17, is a frameshift mutation leading to a truncated protein (Figure 3D), which qualifies as pathogenic very strong (PVS1) evidence of ACMG criteria. Protein structure analysis of NHLRC2 showed that the p.L537Ffs*17 variant leads to an incomplete protein structure beyond the sixth NHL-repeat in the beta-propeller domain (Figure 3D).