PMC3014749_01
Wright stain of peripheral blood smear of CHS patients, showing polymorphonuclear leukocytes with giant granules (200x). (a) Patient 1, (b) patient 2, and (c) patient 3.
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Giant granules were observed in polymorphonuclear cells from these three patients (Figure 1).
Hair shafts under light microscopy (200x). (a) Hair sample of normal Japanese control, showing evenly distributed pigment. (b) Patient 1, (c) Patient 2, (d) Patient 3. Hair shafts of CHS patients showing atypical granular pigment pattern.
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fig2
They all had albinism of the skin and hair (Figure 2).
PMC3014749_02
Hair and skin of patient 4 at the age of 4, showing silvery hair and hypopigmentaion of skin.
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Patient 4 was a 6-year-old female with visual disturbance and hypopigmentation of the skin and hair (Figure 3).
Bone marrow aspirate smear of patient 4, showing (a) myeloperoxidase-positive giant granules and (b) hemophagocytosis.
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The diagnosis of CHS was determined by the presence of myeloperoxidase-positive giant granules in leukocytes (Figure 4(a)). At the age of 4, she suffered from hemophagocytic lymphohistiocytosis (Figure 4(b)), which is known as accelerated phase.
PMC3014749_03
The cDNA sequence patterns of CHS1 mutations. (a) Patients 1, 2, and 3: frameshift mutation in exon 18, c.5541-5542delAA, p. Q1847fsX1850. These three patients were siblings. The same sequence pattern of cDNA was observed in their father. (b) patient 4: Frameshift mutation in exon 10, c.3944-3945 ins C, p.T1315fsX1331. (c) patient 5: Nonsense mutation in exon 30, c.7982 C > G, p.S2661X. (d) patient 5: Nonesense mutation in exon 31, c.8281 A > T, p.R2761X.
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In patients 1, 2, and 3, a two-base deletion (c.5541-5542 del AA) in exon 18 resulted in a frameshift mutation that eventually led to the formation of a stop codon (p.Q1847fsX1850) (Figure 5(a)). In patient 4, we detected a heterogenous one-base (C) insertion (c.3944-3945 ins C) in exon 10, resulting in a frameshift mutation that led to the formation of a stop codon (p.T1315fsX1331) (Figure 5(b)). In patient 5, two heterogenous mutations were identified; C-G substitution (c.7982 C > G) in exon 30 resulted in a nonsense mutation (p.S2661X) (Figure 5(c)), and A-T substitution (c.8281A > T) in exon 31 resulted in a nonsense mutation (p.R2761X) (Figure 5(d)).