PMC7662064_01
A: We present the family pedigree of Patient 1. The proband is denoted by an arrow. We had clinical data, including fat distribution on the patient's son. B: The phenotypic features of Patient 1 are shown. She had the loss of subcutaneous fat deposits in the forearms, lower limbs, and buttocks. She had excess fat deposition around the face, neck, and trunk, although that around the face and neck has been covered with gray paper for privacy reasons. Figure 1A and 1B were presented in our previous report (9).
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We assessed the body fat distribution in Patient 1 at the age of 48 years using DEXA and MRI studies, as shown in Fig. 1B, Fig. 2, and Table 3. We show the family pedigree of Patient 1 in Fig. 1A.
The Figure shows magnetic resonance imaging (MRI) results for Patient 1. A: Thoracic MRI taken at the level of the seventh thoracic vertebrae (left panel) and abdominal MRI taken at the umbilical level (right panel) showed the preservation of subcutaneous fat in the thoracic and abdominal regions. B: A T1-weighted MRI taken at the level of gluteal fat indicated the prominent loss of gluteal subcutaneous fat, indicated by arrows. C: MRI taken at the level of the thigh (upper panel) and calf (lower panel) revealed the nearly complete absence of subcutaneous fat, particularly in the antero-lateral and posterior thigh regions and the entire circumference of the calf regions, indicated by arrows. D: MRI taken at the level of the arms (upper panel) and forearms (lower panel) revealed the marked loss of subcutaneous fat, particularly in the antero-lateral and posterior forearms, indicated by arrows, and the preservation of fat in the arms. Brain MRI, which had been performed when Patient 1 was transferred to the emergency room for convulsions at 40 years of age, showed an old infarction in the right frontal lobe (Fig. 2E), while brain magnetic resonance angiography (MRA) showed severe narrowing at the terminal portions of both sides of the internal carotid artery (Fig. 2F). Narrowing in the proximal regions of both sides of the anterior cerebral and middle cerebral arteries is indicated by black arrows.
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Her brain MRI (Fig. 2E) and MRA (Fig. 2F) findings showed severe narrowing at the end of the internal carotid artery on both sides with an old cerebral infarction in the right anterior lobe.
PMC7662064_02
A: We present the family pedigree of Patient 2, according to the patient's interview. The proband is denoted by an arrow. B: The phenotypic features of Patient 2 are shown. She had the loss of subcutaneous fat deposits in the forearms, lower limbs, and buttocks. She had excess fat deposition around the face, neck, and trunk, although that around the face and neck has been covered with gray paper for privacy. Figure 3B were presented in our previous report (10).
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As shown in Fig. 3B, Fig. 4, and Table 3, she had subcutaneous fat loss in her lower limbs, accompanied by excess subcutaneous fat in the trunk. According to the patient's interview, we show the family tree of Patient 2 in Fig. 3A.
A-E were presented in our previous report (10). Patient 2 was a 69-year-old woman with a BMI of 25.5 kg/m2. A: Thoracic MRI at the level of the seventh thoracic vertebrae (left panel) and abdominal MRI at the umbilical level (right panel) are shown. Thoracic and abdominal MRI revealed the preservation of subcutaneous fat in the thoracic and abdominal regions of Patient 2. B: T1-weighted MRI at the middle level of the gluteus are shown. MRI at the middle level of the gluteus in the proband revealed a decreased amount of gluteal subcutaneous fat, indicated by arrows. C: MRI at the middle level of the thigh (upper panel) and calf (lower panel) in Patient 2 are shown. The patient had the marked loss of subcutaneous fat, particularly in the antero-lateral and posterior thigh regions, indicated by arrows, although subcutaneous fat in the internal thigh region remained. She had the near-complete loss of subcutaneous fat in the antero-lateral and posterior calf regions, indicated by arrows; however, very little subcutaneous fat in the internal calf region remained. D: MRI at the middle level of the left arm (left panel) and forearm (right panel) are shown. Axial MRI at the level of the arm revealed the preservation of subcutaneous fat. Axial MRI at the level of the forearm revealed the almost complete absence of subcutaneous fat in the antero-lateral forearm, indicated by arrows; however, the preservation of subcutaneous fat in the internal forearm was observed. As shown in Fig. 4E, brain MRI at the age of 69 years showed old cerebral infarction in the area of the left frontal lobe and temporal lobe, to which blood is supplied by the left middle cerebral artery. As shown in Fig. 4F, MRA demonstrated a narrowing at the left internal carotid artery (blue arrow), occlusion of the left anterior artery (red arrow), and a marked narrowing in the horizontal region of the left middle cerebral artery (yellow arrow) with occlusion in the distal region of the left middle cerebral artery (white arrow).
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As shown in Fig. 4E, her brain MRI at 69 years of age revealed an old cerebral infarction in the area of the left frontal lobe and temporal lobe, to which blood is supplied by the left middle cerebral artery. As shown in Fig. 4F, MRA showed a narrowing at the left internal carotid artery, occlusion of the left anterior artery, and a marked narrowing in the horizontal region of the left middle cerebral artery with occlusion in the distal region of the left middle cerebral artery.
Reversed sequencing chromatograms showed the c.14576 G>A heterozygous mutation (p.R4810K) in the mysterin gene. A: Patient 1, B: Patient 2
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By direct sequencing, we confirmed p.R4810K in Patient 1 and Patient 2, as shown in Fig. 5.