Kihei Maekawa

Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature

AbstractWe report a male infant with multiple congenital anomalies and mosaic variegated aneuploidy; a rare cytogenetic abnormality characterized by mosaicism for several different aneuploidies involving many different chromosomes. He had prenatal-onset growth retardation, microcephaly, dysmorphic face, seizures, hypotonia, feeding difficulty, and developmental delay. In addition, he developed bilateral Wilms tumors. Neuroradiological examination revealed Dandy-Walker malformation and hypoplasia of the cerebral hemisphere and pons. Cytogenetic analysis revealed various multiple numerical aneuploidies in blood lymphocytes, fibroblasts, and bone marrow cells, together with premature centromere division (PCD). Peripheral blood chromosome analysis from his parents also showed PCD, but no aneuploid cells. The clinical phenotype and multiple aneuploidies of the patient may be a consequence of the homozygous PCD trait inherited from his parents. Comparison with previously reported cases of multiple aneuploidy suggests that mosaic variegated aneuploidy with PCD may be a clinically recognizable syndrome with major phenotypes being mental retardation, microcephaly, structural brain anomalies (including Dandy-Walker malformation), and possible cancer predisposition.

Characteristics of gene mutations among 32 unrelated Japanese Gaucher disease patients : absence of the common Jewish 84GG and 1226G mutations

The prevalence of seven different mutations (84GG, IVS2+1, 754A, 1226G, 1342C, 1448C, and 1504T) was investigated in 32 unrelated Japanese Gaucher patients of which 20 were type I, 6 were type II, and 6 were (type III). These mutations constitute 95% of the mutations observed in Jewish patients with Gaucher disease and 75% of the mutations in non-Jews (European). The most frequent mutation, 1448C (L444P), accounted for 26 alleles (40.6%); the second most prevalent mutation was 754A (F213I), accounting for 7 alleles (10.9%); 27 alleles (42.2%) were unidentified. To data, neither the 1226G (N370S) nor 84GG mutations have been identified in the Japanese population though these alleles account for approximately 70% and 10% of mutations in the Jewish population. These data suggest that mutant alleles identified from the Japanese population are distinct from those observed in Jewish and non-Jewish (European) patients with Gaucher disease.

Mutation prevalence among 47 unrelated Japanese patients with Gaucher disease: identification of four novel mutations.

Utilizing PCR and PCR-SSCP analysis we investigated the prevalence of glucocerebrosidase gene mutations in 47 unrelated Japanese patients with Gaucher disease. Sixty alleles (63.8%) and 20 alleles (21.3%) were identified by analysis for common mutations and PCR-SSCP analysis, respectively. The L444P and F213I mutations were common, accounting for 41 alleles (43.6%) and 14 alleles (14.9%). R496C, D409H, S366G and 1447-1466 del ins TG mutations were identified in 5, 3, 3 and 3 alleles, respectively. The other mutations were unique. In spite of vigorous screening, 14 alleles (14.9%) could not be identified. Four novel mutations were identified by PCR-SSCP analysis: G189V, S366G, K413Q and R433G. These data indicate that besides the L444P mutation no other frequent mutation is present and there is broad heterogeneity of the glucocerebrosidase gene mutations in Japanese patients with Gaucher disease.

Rapid identification of mutations in the glucocerebrosidase gene of Gaucher disease patients by analysis of single-strand conformation polymorphisms

To detect mutations in the glucocerebrosidase gene in Gaucher disease patients, we used the recently described technique of single-strand conformation polymorphism (SSCP) analysis in combination with selective amplification. We analyzed exon 8, 9, 10 and 11 of the glucocerebrosidase gene; these exons were sequentially amplified using the selectively amplified products as templates. We found variant SSCP patterns corresponding to the presence or absence of the 6433C mutation, which was detected by NciI digestion analysis, in exon 10. Furthermore, we detected four variant SSCP patterns in exon 8, 10 and 11. Sequencing analysis consistently revealed four single-base substitutions in the corresponding exons, three novel missense mutations (5409A, 6375G and 6682T) and one silent polymorphism (6594A). These mutations were found only in one patient; therefore, these findings have confirmed the marked genetic heterogeneity of Gaucher disease. SSCP analysis in combination with selective amplification is a rapid and sensitive procedure for the screening of the mutations in the glucocerebrosidase gene of patients with Gaucher disease.

GC/MS analysis of urinary excretion of 9alpha,11beta-PGF2 in acute and exercise-induced asthma in children

9α,11β‐Prostaglandin (PG) F2 is an initial metabolite of PGD2 which has a potent bronchoconstrictive activity.

Psychiatric inpatients and chromosome deletions within 22q11.2.

Velocardiofacial syndrome (VCFS) is a congenital disorder characterised by multiple dysmorphisms, cleft palate, cardiac anomalies, and learning disabilities due to a microdeletion of chromosome 22q11.2. Although VCFS is often associated with psychiatric symptoms, its prevalence among psychiatric patients is unknown.  A total of 326 patients admitted in September and October 1997 to a Japanese psychiatric hospital were screened for the clinical features of VCFS. Twelve patients with minor facial dysmorphia were identified; chromosomal analysis with fluorescent in situ hybridisation (FISH) was performed in six patients who, further assessment suggested, were most likely to have VCFS.  Chromosome 22q11.2 deletion was identified in a 41 year old woman who had symptoms of schizophrenia but no major dysmorphia, such as cardiovascular anomalies and cleft palate. Her behavioural and neuropsychological profiles were similar to those previously reported in VCFS. She was hemizygous for the FISH probe N25 (GDB locus D22S75) and also for probes N72H9 (D22S181), sc11.1a, C443 (D22S941), sc4.1 (D22S134), sc11.1b, N19B3 (D22S264), N122B5 (D22S934), and N77F7 (D22S939). The size of the deletion was about 3 Mb.  Our patient had only some features of VCFS including a square nasal root, hypernasal speech, and hypoparathyroidism. She did, however, have the common larger deletion of type A. This finding suggests that psychiatric symptoms in VCFS can occur without major developmental symptoms such as cardiovascular anomalies and cleft palate. Additional patients with schizophrenia may have subtle features of VCFS which are unrecognised on routine medical examinations.

Severe skeletal complications in Japanese patients with type 1 Gaucher disease

To better characterize skeletal complications in Japanese patients with type 1 Gaucher disease (GD), we performed genotyping and clinical and radiological analysis of 35 patients, the vast majority of this population, Skeletal complications tend to be very common, severe and rapidly progressive in Japanese patients with type 1 GD. Twenty (57%) of these patients manifested end points of severe bone disease including avascular necrosis, pathological fracture and/or bone crisis. Mean time from presentation/diagnosis of GD until presentation of this involvement was 3 years 6 months±4 years 1 month. Prevalence of severe bone disease is significantly higher in splenectomized than in non-splenectomized patients – 81% (17/21) versus 21% (3/14) (p=0.0007, Fishers exact test). Four (29%) of 14 patients receiving enzyme replacement therapy (ERT) or bone marrow transplantation (BMT) manifested severe bone involvement for the first time during or after treatment. All cases occurred in children in whom ERT doses had been lowered after only brief administration of higher starting doses (n=3) or partial donor marrow engraftment resulted in low glucocerebrosidase (GCR) activity (n=1). These observations suggest that splenectomy may correlate with accelerated skeletal deterioration with severe skeletal disease, at least in patients with severe phenotypic expression. They also suggest that it is important that sufficient GCR is available in paediatric patients with severe phenotypic expression. Hence ERT dosages should be based on disease severity and on age, with sustained administration of full doses in patients at greater risk of important skeletal complications.

An accumulation of galactocerebroside in kidney from mouse globoid cell leukodystrophy (twitcher).

Abstract The twitcher mouse is genetically determined mutant characterized by a deficiency of galactocerebroside beta-galactosidase. In this study, a significant accumulation of galactocerebroside was demonstrated in twitcher mouse kidney. The data suggest that mouse Krabbes disease is not only involved in CNS, but also in visceral organs.

Computed tomography in tuberous sclerosis: — With special reference to relation between clinical manifestations and CT findings —

Concerning the clinical signs and symptoms, we noticed skin white macula in 87%, adenoma sebaceum in 53%, mental retardation in 75%, retinal phacoma in 54% and seizure in 92%. Numbers of nodules ranged from zero to 11, and showed no correlation with aging. Half of the cases showed slight ventricular dilatation, one quarter showed moderate dilatation and the remainder were normal. There was no definite correspondence between size of the ventricle and number of nodules. There were relatively many cases with normal mental state in the group with normal ventricles. In adult cases a large ventricle does not always mean poor prognosis in mental state. Almost all of the cases with cortical atrophy had mental retardation. In the group with moderate dilatation infantile spasms were the most frequent type of seizure. On the contrary, grand mal was most frequent in the normal group. As for the position of nodules there was no difference between the normal and dilated groups. Nodules were predominantly seen in the lateral aspect of the body, trigone of the lateral ventricle and adjacent to the foramen of Monro. Asymmetrical lateral ventricles were noticed in 18%. Incidence of laterality increased as dilatation proceeded. It was larger on the left side in 9 out of 11 cases. We have no reasonable explanation of this tendency. There was one case with a tumor which was verified by enhanced CT. There were five cases with brain anomalies.

Major Dermatophagoides mite allergen, Der 1, in soft toys.

Background Allergen avoidance is recommended when treating atopic asthma. Objectives Soft toys are often kept in close proximity to children and may serve as a source of exposure. Due to the potential danger from the mite allergen content of these toys, Der 1 from toys was measured.