PMC4302186_01
Pedigree, sequencing analysis, and distal sural nerve biopsy of the proband with compound heterozygous mutations in PRX. A: Pedigree of patient's family. Genotypes of both PRX mutations were indicated at the bottom of each examined individual. Open symbols, unaffected; filled symbol, affected; half-filled symbols, individuals possessing only a heterozygous mutation; asterisk, whole-exome sequencing performed; and arrow, proband. B: Sequencing chromatograms from the proband and her parents. Vertical arrows indicate the mutation site. * (asterisk) and X indicate the mutation codon in I-2 and and I-1, respectively. C: Transverse semi-thin sections with toluidine blue stain (x400). Light microscopy images revealed nerve fascicles that were markedly decreased in size, diffuse subendoneurial edema, and moderately to markedly decreased numbers of myelinated fibers (MFs) of all calibers with suggestive onion bulb formation and endoneurial fibrosis. D: Histogram of the sural nerve biopsy showing a unimodal distribution pattern. The mean diameter of MF (3.14 microm) and the percentage area of MFs (1.39%) were lower than in age-matched controls. E and F: Ultrastructural micrographs by electron microscopy (x1,000) revealed findings consistent with demyelinating neuropathy, such as focally folded, uncompacted, or deteriorating myelin, irregular myelin thickness, and fragmented myelin structures in Schwann cells or nearby macrophages.
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F1
A 10-year-old girl (Fig. 1A, II-3) was the third child with two healthy older sisters born to nonconsanguineous parents (FC390). Light-microscopy examination of longitudinal and cross-sections of nerve fibers revealed nerve fascicles that were markedly decreased in size, diffuse subendoneurial edema, and moderately to markedly decreased numbers of myelinated fibers (MFs) of all calibers, with suggestion of onion-bulb formation and endoneurial fibrosis (Fig. 1C). The mean diameter of MFs (3.14 microm) and the percentage area of MFs (1.39%) were also lower than in age-matched controls (4.5 microm and 25.2%, respectively) (Fig. 1D). Electron-microscopy examination revealed findings consistent with abnormal myelin, such as focally folded, uncompacted, or deteriorating myelin, irregular myelin thickness, or fragmented myelin structures in Schwann cells or nearby macrophages (Fig. 1E and F). The c.1174C>T and c.2035C>T mutations were inherited from the patient's mother and father, respectively (Fig. 1B).
Hip, thigh, and lower calf MRIs of the proband (II-3) with PRX mutation. A: Coronal scan of lower limbs. T1-weighted images demonstrated no definite fatty or atrophic changes in hip and thigh muscles. B-E: Axial scans of lower limbs. B and C: At the thigh levels, MR images were normal. D and E: On the lower calf levels, we found mild fatty changes in distal peronei muscles (arrows), but, the tibialis anterior and soleus muscles were not involved.
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F2
A 10-year-old girl (Fig. 1A, II-3) was the third child with two healthy older sisters born to nonconsanguineous parents (FC390). MRI scans of the hip and thigh were normal (Fig. 2A, B, and C). Lower-calf MRI revealed hyperintense signal abnormalities (Fig. 2D and E).