Mutations in COG2 encoding a subunit of the conserved oligomeric golgi complex cause a congenital disorder of glycosylation.

The conserved oligomeric Golgi (COG) complex is involved in intra-Golgi retrograde trafficking, and mutations in six of its eight subunits have been reported in congenital disorders of glycosylation (CDG). Here we report a patient showing severe acquired microcephaly, psychomotor retardation, seizures, liver dysfunction, hypocupremia, and hypoceruloplasminemia. Analysis of his serum glycoproteins revealed defects in both sialylation and galactosylation of glycan termini. Trio-based whole-exome sequencing identified two heterozygous mutations in COG2: a de novo frameshift mutation [c.701dup (p.Tyr234*)] and a missense mutation [c.1900T > G (p.Trp634Gly)]. Sequencing of cloned reverse-transcription polymerase chain reaction (RT-PCR) products revealed that both mutations were located on separate alleles, as expected, and that the mutant transcript harboring the frameshift mutation underwent degradation. The c.1900T > G (p.Trp634Gly) mutation is located in a domain highly conserved among vertebrates and was absent from both the public database and our control exomes. Protein expression of COG2, along with COG3 and COG4, was decreased in fibroblasts from the patient. Our data strongly suggest that these compound heterozygous mutations in COG2 are causative of CDG.

Cutaneous polyarteritis nodosa: therapy and clinical course in four cases.

Cutaneous polyarteritis nodosa (PN) has a benign and chronic course; relapses are frequently associated with steroid dependence. We have observed four cases of cutaneous PN in the past 15 years and followed up two of the four cases long-term for 13 and 10 years after diagnosis. There has been a marked contrast in the clinical courses of these two cases: one case has shown a complete remission for 12.5 years without treatment during the most recent 11 years; the other case had four relapses and has never experienced cessation of treatment. The only difference between the two cases was careful therapy with adequate prednisolone in the long-term remission case. The other two cases clinically showed erythema nodosum-like features, and they had antecedent sore throats and embedded chronic tonsillitis; one was associated with presumed streptococcal infection. These two cases may simply be an accelerated process of post-streptococcal erythema nodosum rather than typical cutaneous PN. We performed tonsillectomies as adjuvant therapy in these two cases. No relapse of the disease has been observed in these two cases, and the tonsillectomy allowed us to taper the dose of steroids, resulting in discontinuation of the treatment in one of the two cases. The duration of the remission as well as the adjuvant therapy was variable in each of our cutaneous PN cases. Tonsillectomy can be recommended as an adjuvant to steroids for PN cases with chronic tonsillitis and/or streptococcal infection.

Sebaceous carcinoma, trichoblastoma, and sebaceoma with features of trichoblastoma in nevus sebaceus.

A 73-year-old woman had a linear yellowish plaque on the upper part of her right ear since birth. She presented because of the sudden growth of a nodule within the plaque. The plaque was waxy and yellowish, arching around the upper part of the ear. A reddish to yellowish large nodule was seen within the central part of the arc-shaped plaque; in addition, a small pigmented nodule, a small skin-colored nodule, and a few pigmented papules were observed in the anterior half of the arched plaque. Histopathologic examination revealed the large nodule to be sebaceous carcinoma, the small pigmented nodule to be trichoblastoma, the small skin-colored nodule to be sebaceoma with the features of trichoblastoma, a few pigmented papules to be superficial trichoblastomas due to primitive follicular induction, and the linear yellowish plaque to be nevus sebaceus. Although our literature search revealed scanty reports of definite cases of sebaceous carcinoma in nevus sebaceus, the presented case demonstrated the occurrence of sebaceous carcinoma in nevus sebaceus. Malignant neoplasms occurring in nevus sebaceous seem to be extremely rare, but care should be taken when a large nodule suddenly grows in a lesion of nevus sebaceus, especially in older adults. The presented case also suggested a close relation between trichoblastoma and sebaceoma. The cytokeratin staining pattern could not distinguish between sebaceous and follicular neoplasms in our case.

Ketoacidosis accompanied by epileptic seizures in a patient with diabetes mellitus and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

We herein report a rare case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and diabetes mellitus with ketoacidosis. An 18-year-old female patient was diagnosed to have diabetes mellitus and insulin therapy was thereafter initiated. At 26 years of age, she was hospitalized for diabetic ketoacidosis, soon followed by a loss of consciousness, left-sided dysmetria, and ataxic speech. MELAS was diagnosed because of the presence of ragged red fibers in a muscle biopsy. At 33 years of age, she was admitted to our hospital because of ketoacidosis and partial status epilepticus. A blood gas examination revealed as follows; arterial pH, 6.88; bicarbonate, 2.1 mmol/l; base excess - 29.8 mmol/l. The serum level of glucose had also increased to 30 mmol/l. The serum levels of lactate and B-hydroxybutyrate were elevated to 11.4 mmol/l and 1,990 micromol/l, respectively. Ketoacidosis improved by fluid replacement and continuous intravenous insulin infusion. A brain MRI demonstrated hyperintensity areas on FLAIR images in the bilateral temporal lobes and the cerebellum. A proton MRS demonstrated the abnormal lactate accumulation in the bilateral temporal and occipital lobes. Since epileptic seizures are rare in patients with diabetic ketoacidosis, such seizures may indicate the existence of MELAS syndrome.

Localized soft tissue angiomatosis with subsequent development of angiolymphoid hyperplasia with eosinophilia.

We report an unusual case of arteriovenous (AV) malformation (localized form of soft tissue angiomatosis): a reaction of angiolymphoid hyperplasia with eosinophilia (ALHE) developed over the lesion of this pre-existing AV malformation. To the best of our knowledge, there is no other report of ALHE in association with a pre-existing bona fide AV malformation. A 71-year-old woman consulted our clinic because a reddish, dome-shaped tumor on her preauricular region, present as a slightly elevated, skin-colored tumor since her childhood, had rapidly enlarged and become more elevated with color change during the preceding two months. The histological features of most of the lesion corresponded to those of soft tissue angiomatosis (localized form). The proliferative vessels underlying the soft tissue angiomatosis streamed out and welled into the dermis with an accompanying prominent inflammatory infiltrate composed of lymphoid cells and eosinophils: these histological features were characteristic of ALHE. The recent abrupt clinical changes in the tumor were considered to represent a reaction to the angiomatosis with development of ALHE.

[A case of mandibular retromolar canal: elements of nerves and arteries in this canal].

The large bilateral mandibular retromolar canals were found in a 47-year-old Japanese man. This paper presents the nature and distribution of the elements of nerves and arteries in the left retromolar canal which were able to examined. The left mandibular retromolar canal arose from the bifurcation of the mandibular canal at 18 mm anterior to the mandibular foramen and it opened on the surface of the retromolar fossa at 13 mm posterior to the third mandibular molar. The total length of the retromolar canal from the bifurcation to the retromolar foramen was about 16 mm, and 2.5-2.6 mm in diameter. The radiographic image of this retromolar canal was a liner shadow with thin radiopaque anterior and posterior borders cast on a lateral radiography of the left half of the head. Within the retromolar canal, the artery that was branched from the inferior alveolar artery ran through the canal forwards and joined with the branches of the buccal artery and the facial artery, and then gave off the superior and inferior labial arteries. The nerve (R. retromolaris) in the retromolar canal derived from the inferior alveolar nerve trunk and branched off to the following areas: the third mandibular molar, the mucosa of retromolar triangle, the buccal mucosa, and the buccal gingiva of the mandibular premolar and molar region. The retromolar canals and foramina were found in 8 out of 41 Japanese skulls. Clinically, if the arteries in the retromolar canal become injured, complications may arise such as bleeding, and iatrogenic nerve damage may lead to paralysis.(ABSTRACT TRUNCATED AT 250 WORDS)