PMC10043213_01
PMC10043213_02
PMC10043213_03
PMC10043213_04
PMC10043213_05
Changes in patients' routine blood examination. (A) Changes in patients' RBC levels. (B) Changes in patients' PLT levels. (C) Changes in patients' Hb levels. (D) Changes in patients' WBC levels. *Transfusion treatments: Patient 1 received RBC 0.25 U; Patient 4 received PLT 0.75 U.
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F1
Routine blood tests in Patients 1 and 4 showed that RBC, PLT, and Hb always remained below normal levels (Figures 1A-C). WBC findings in Patient 4 were always higher than normal, possibly associated with recurrent respiratory infections (Figure 1D).
Patient x-rays. (A) Patient 1: significant increase in bone density observed at skull base (arrow). (B) Patient 1: vertebral endplate showed typical "sandwich vertebrae" appearance. (C) Patient 2: generalized increase in bone density and typical pelvic wing "bone-in-bone" evident (arrow); high-bone density under the cartilage in the pelvis (arrow). (D) Patient 2: diffusely increased bone density confirmed and osteopetrosis in the distal metaphysis of the femur showed typical "bone-in-bone" appearance (arrow). (E) Patient 3: head mass was identified with a hard quality and swelling around the frame and uneven bone density detected. (F) Patient 3: vertebral endplate showed typical "sandwich vertebrae" appearance. (G) Patient 4: diffuse increase in bone density at the upper radius (arrow), showing "bone-in-bone" appearance. (H) Patient 4: vertebral endplate appeared thickened, with "sandwich vertebrae". (I) Patient 4: observed osteopetrosis in skull base (arrow). (J) Patient 4: lateral skull computerized tomographyshowing increased thickness of skull base (arrow). (K-L) Patient 3: marrow biopsy results showed partial calcification of trabecular bone; HE staining x 40 (K); HE staining x 100 (L).
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F2
And marrow biopsy results in patient3 showed partial calcification of trabecular bone (Figure 2).
PMC10043213_06
Family pedigrees and genetic sequencings. (A) Pedigree for each patient. (B) Genetic analysis of the gene mutation in family of Patient 1: compound heterozygous variants c. 880T > C(p. F294V) and c. 686C > G(p. S229X) in the CLCN7 gene. Homologous sequences of CLCN7 across species (C). A cross-species alignment of amino acid sequences showed that p. F294V and p. N190S variants occur in a highly conserved region.
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F3
And each patient the variants are inherited from their parents (Figure 3).