Fig. 1: Individual photographs, pedigrees, and genotypes; schematic representation of CLPB ___domain structure; neuroimaging findings; and peripheral blood smear and bone marrow aspirates of CLPB de novo patients. | Genetics in Medicine

Fig. 1: Individual photographs, pedigrees, and genotypes; schematic representation of CLPB ___domain structure; neuroimaging findings; and peripheral blood smear and bone marrow aspirates of CLPB de novo patients.

From: Neutropenia and intellectual disability are hallmarks of biallelic and de novo CLPB deficiency

Fig. 1

a Individual P2 at the age of 9 months. b,c,g Individual P3 at the age of 16 months and 4 and 7 years, respectively. d,e,f Individual P5 at the age of 2 weeks, 3 and 10 years, respectively. h Individual P4 at age 7.8 years. i Pedigrees of all families including the genotype and position of variants in schematic representation of human CLPB. j Magnetic resonance image (MRI) findings in the three individuals (axial T2-weighted and sagittal T1-weighted images). At the age of 17 months, P2 shows supratentorial atrophy and also mild cerebellar atrophy. White matter signal is slightly T2-hyperintense in the central white matter. P3 also shows mild global atrophy with progressive thinning of the cortical ribbon. White matter signal is diffusely abnormal, with normal signal of the corpus callosum and the anterior limb of the internal capsule. At age 3 years, the medial part of the middle cerebellar peduncle has an elevated T2 signal. P5 has diffusely elevated white matter signal, including cerebellar white matter, indicating delayed myelination at age 15 months. At age 7 years, she has developed supratentorial atrophy. Myelination has progressed, but there is still a diffusely abnormal white matter signal. Also the signal in the basal ganglia (head of the caudate nucleus and upper part of the putamen) is too high on the T2-weighted image. Also in P5, the signal of the medial part of the middle cerebellar peduncle is elevated. k Peripheral blood smear (P6) showing relative neutropenia including forms with toxic granulation, reflecting granulocyte colony stimulating factor (GCSF) therapy. Red cell and platelet indices were within normal limits. 1,000× magnification; Wright-Giemsa. l Bone marrow aspirate (P6) shows trilineage hematopoiesis with left-shifted myelopoiesis. Mild dysmyelopoiesis is present, including neutrophils with nuclear hypolobation and megaloblastoid change (inset and solid arrow). Hematogones (B-cell progenitors) are also increased in frequency (cross-hatched arrow), confirmed by flow cytometry. 1,000× magnification; Wright-Giemsa. m The bone marrow (P6) is hypercellular for age showing trilineage hematopoiesis with expanded paratrabecular cuff of left-shifted myeloid cells and mild eosinophilia, changes reflecting GCSF therapy 400× magnification; hematoxylin and eosin (H&E). n The bone marrow aspirate smear (P4) shows a marked increase in immature myeloid and lymphoid progenitor cells. Eosinophils are also increased. Myeloid maturation is megaloblastic with several large immature cells with intermediate amounts of cytoplasm, round eccentrically placed nuclei, prominent nucleoli, perinuclear hofs, smooth chromatin, and sparse but coarse cytoplasmic granulation. o The bone marrow aspirate (P4) demonstrates trilineage hematopoiesis with a decreased myeloid to erythroid ratio. Myeloid cells include promyelocytes and very rare myelocytes but no mature forms. Erythroid maturation is complete. p The bone marrow (P4) is hypercellular for age showing trilineage hematopoiesis with expanded paratrabecular cuff of left-shifted myeloid cells, changes reflecting GCSF therapy 400× magnification; H&E. Scale bars in k,l indicate 50 μm and in M-P 40 μm.

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