Figure 1.
Figure 1. Clinical characteristics of Patient 1. (A) Reduced cellularity is apparent in the marrow biopsy. Hematopoietic activities occupy ∼40% of the space between bones. Surrounding fat tissue is seen. Original magnification ×100. (B) Bone marrow aspirate shows no evidence of dysplasia, cytoplasmic vacuoles, ringed sideroblasts, or excess blasts. Original magnification ×500. (C) Imaging of the pancreas showed hyperechogenicity (arrow) on ultrasonography (imaging of a normal pancreas can be found in supplemental Figure 2D). (D) Computed tomography scan showed hypodense tissue (arrow). The ultrasound and computed tomography images are characteristic features of lipomatosis seen in SDS. (E) Radiograph of the long bones showed irregularity of the metaphyses with areas of sclerosis (black arrow) and lucency (white arrow). Similar images of Patient 3 can be found in supplemental Figure 1. (F) Pedigree of Family 1. (G) Sanger sequencing was done to validate mutations in DNAJC21 (NM_001012339.2) found by whole-exome sequencing. The figure indicates the position of the mutation (c.520) on exon 5. The nucleotide substitution of C by T is seen in homozygous (patient, II-1) and heterozygous (parents, I-1 and I-2) states, consistent with recessive inheritance. The alteration results in premature protein truncation (p.Gln174*). (H) Pedigree of Family 2. (I) Sanger sequencing of portion of exon 2 of DNAJC21 in family members showing segregation of the pathogenic missense variant. (J) Pedigree of Family 3. (K) PCR of genomic DNA from patient 4 showing absence of amplification of exons 5 and 6, and normal amplification of surrounding exons and glyceraldehyde-3-phosphate dehydrogenase control. (L) The DNACJ21 protein with its domains and predicted patients’ mutations are shown. (M) Immunoblots of protein extracts of cells from controls and members of Family 1 (left, peripheral blood T cells), Patient 2 (center, peripheral blood T cells), and Patient 4 (right, marrow fibroblasts) with DNAJC21 and loading control antibodies. Band densitometry was performed with ImageJ software. NT, not tested.

Clinical characteristics of Patient 1. (A) Reduced cellularity is apparent in the marrow biopsy. Hematopoietic activities occupy ∼40% of the space between bones. Surrounding fat tissue is seen. Original magnification ×100. (B) Bone marrow aspirate shows no evidence of dysplasia, cytoplasmic vacuoles, ringed sideroblasts, or excess blasts. Original magnification ×500. (C) Imaging of the pancreas showed hyperechogenicity (arrow) on ultrasonography (imaging of a normal pancreas can be found in supplemental Figure 2D). (D) Computed tomography scan showed hypodense tissue (arrow). The ultrasound and computed tomography images are characteristic features of lipomatosis seen in SDS. (E) Radiograph of the long bones showed irregularity of the metaphyses with areas of sclerosis (black arrow) and lucency (white arrow). Similar images of Patient 3 can be found in supplemental Figure 1. (F) Pedigree of Family 1. (G) Sanger sequencing was done to validate mutations in DNAJC21 (NM_001012339.2) found by whole-exome sequencing. The figure indicates the position of the mutation (c.520) on exon 5. The nucleotide substitution of C by T is seen in homozygous (patient, II-1) and heterozygous (parents, I-1 and I-2) states, consistent with recessive inheritance. The alteration results in premature protein truncation (p.Gln174*). (H) Pedigree of Family 2. (I) Sanger sequencing of portion of exon 2 of DNAJC21 in family members showing segregation of the pathogenic missense variant. (J) Pedigree of Family 3. (K) PCR of genomic DNA from patient 4 showing absence of amplification of exons 5 and 6, and normal amplification of surrounding exons and glyceraldehyde-3-phosphate dehydrogenase control. (L) The DNACJ21 protein with its domains and predicted patients’ mutations are shown. (M) Immunoblots of protein extracts of cells from controls and members of Family 1 (left, peripheral blood T cells), Patient 2 (center, peripheral blood T cells), and Patient 4 (right, marrow fibroblasts) with DNAJC21 and loading control antibodies. Band densitometry was performed with ImageJ software. NT, not tested.

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