Hiroshi Kimoto

Probable assignment of soluble isocitrate dehydrogenase (IDH1) to 2q33.3

SummaryGene dosage effects for soluble isocitrate dehydrogenase (IDH1) were investigated in four unrelated cases with abnormalities involving the long arm of chromosome 2. Case 1 was trisomic for 2q33.3→qter, Case 2 monosomic for 2q33.3→q35, Case 3 trisomic for 2q11.2→q24.2, and Case 4 monosomic for 2q23→q24.2. These abnormalities were de novo except in Case 1, where trisomy 2q resulted from a maternal translocation. The red cell IDH1 levels were significantly reduced in Cases 1 (41.4% of normal value) and 2 (51.9%), while they were normal in Cases 3 and 4. The low IDH1 level also in the father of Case 1 (43.6%), together with the common electrophoretic phenotype of IDH1 in red cells as well as leukocytes, led us to suppose that Case 1 was really heterozygous for common and probable null alleles, and that the IDH1 gene locus could be excluded from 2q33.3→qter. On the other hand, normal IDH1 values in the parents of Case 2 were consistent with the hemizygosity for this locus in Case 2. The results suggested that the IDH1 locus could be assigned to the 2q33.3 band, especially the proximal portion of it.

Probable inverted tandem duplication of Xp in a 46,Xp+Y boy

SummaryA mentally retarded 16-month-old boy with subnormal stature, strabismus, anteverted nares and deformed ears was found to have a de novo structural rearrangement of the X chromosome (46,Xp+Y). The banding patterns of the abnormal X chromosome were interpreted to be an inverted tandem duplication of the segment Xp22.1→Xp22.3. Several other possibilities were considered but thought less likely. DNA replication studies with BrdU incorporation revealed the replication pattern of the duplicated segment to be similar to the equivalent portion of the X chromosome.

Mumps-induced opsoclonus-myoclonus and ataxia

A 9-year-old boy manifested acute cerebellar ataxia associated with mumps infection. He developed opsoclonus, myoclonus, tremor, and truncal ataxia 7 days after mumps infection. Lumbar puncture revealed pleocytosis without elevation of protein; ELISA demonstrated an increased IgM titer of cerebrospinal fluid against mumps virus. From these results it was determined that acute cerebellar ataxia was induced by a direct invasion of mumps virus. Electroencephalography demonstrated normal background activity, although alpha-like activity appeared bilaterally in the frontal regions which was induced by eye closure and decreased by eye opening. Polygraphic electroencephalography revealed that the alpha-like activity corresponded to the ocular movement recorded above or lateral to the eyelids by electro-oculography; therefore, the alpha-like activity was considered to be derived from the opsoclonus which was secondary to cerebellar involvement. His neurologic symptoms improved gradually and resolved completely within 3 months after the onset of acute cerebellar ataxia.

Assignment of ABO locus to 9q31.3----qter by study of a family in which an intrachromosomal shift involving chromosome 9 is segregating

SummaryA family in which an intrachromosomal shift, dir ins(9) (q22.1q31.3;q34.3), was segregating is described. A meiotic crossing over in the noninsertional loop of the carrier mother appeared to have resulted in the proband with a recombinant chromosome 9 duplicating the interstitial segment 9q22.1→q31.3. The study of ABO and AK1 phenotypes in the family showed that the proband was also a recombinant for the ABO locus. These results allowed us to assign the ABO locus to 9q31.3→qter on the cytogenetic basis.

Duplication of 2p25: confirmation of the assignment of soluble acid phosphatase (ACP1) locus to 2p25

SummaryThe regional localization of the gene coding for soluble acid phosphatase (ACP1) has been under debate in the two different chromosome regions, 2p23 or 2p25. Gene dosage studies in a case with a karyotype of 46,XX,dir dup(2) (p25.1→p25.3) showed that the ACP1 activity was increased to 1.4 times the mean value of normal individuals with the same ACP1 phenotype, while the level of soluble malate dehydrogenase (MDH1) was normal. These gene dosage effects indicated that the ACP1 gene locus can be mapped to 2p25.

Farber's disease (disseminated lipogranulomatosis)--a pathological, histochemical and ultrastructural study--.

The first case of Farbers disease in Japan was reported, which was confirmed clinically, biochemically and pathologically. Soon after birth, the patient started developing hoarseness, stridor, fever, muscle hypotonous with retarded psychomotor functions including incapability of sitting alone and head control, joint swelling, subcutaneous nodules, albuminocytologic dissociation in cerebrospinal fluid, nodular corneal opacity, and abnormal findings in electroencephalogram. Lipid analysis on the material obtained from a subcutaneous nodule confirmed the presence of ceramide. Pathologically, the subcutanoues nodules were made up of granulomatous lesions displaying varied histological pictures, i.e., from cellular to fibrous areas depending on the disease progress. In the beginning, cells were mostly spindle‐shaped, and as these cells were getting more round and larger, cells manifested the morphology of foam cells. Spindle‐shaped cells were positive for periodic acid‐Schiff and acid mucopolysaccharide stainings. This particular substance disappeared almost entirely in typical foam cells. Electron microscopically, the cytoplasm of foam cells was filled with membrane‐bound storage inclusions which consisted of so‐called curvilinear tubular structures. Morphogenesis of the granulomatous lesions and histochemical and ultrastructural correlation of storage cells in this disorder were discussed.

A case of a reciprocal translocation between the Y and No. 1 chromosomes

SummaryA reciprocal translocation between the Y and No. 1 chromosomes was found in a male infant with psychomotor retardation and infantile spasms. The karyotype was designated as 46,X,t(1; Y) (q21; q11) on the basis of G- and Q-banding analyses. Previously reported cases with Y/autosomal translocations are reviewed.

The critical monosomic segment involved in 4p- syndrome: A high-resolution banding study on five inherited cases

SummaryIn an attempt to determine the critical monosomic segment involved in 4p- syndrome, we studied the precise breakpoints of five inherited cases with the syndrome using a high-resolution banding technique. The 5 patients ranged in age at diagnosis from newborn to 15 months, 4 of whom could be clinically diagnosed as having 4p- syndrome. Common clinical features included mental retardation, low birth weight, growth failure, hypotonia, microcephaly, peculiar facial dysmorphia and ear malformations. Karyotypes of the 5 were 46,XX,−4,+der(4),t(4;21) (p16.1;q22.3)pat; 46,XX,−4,+der(4), inv ins(4;9)(p15.32p16.3;q34.3)pat; 46,XX,rec(4),del p,inv(4)(p15.2q35)pat; and 46,XX,−4,+der(4),t(4;18) (p15.2;p11.21)mat (two cases, related). The results suggested that monosomy for the proximal half of the 4p16 band is sufficient to express 4p-syndrome.

Interstitial deletion of the long arm of chromosome 2: A case report and review of the literature

SummaryA girl with mental retardation and multiple anomalies was shown to have a de novo interstitial deletion of the long arm of chromosome 2(2q23.3→q24.2) by the use of high resolution banding technique. Review of the literature revealed that her clinical features resembled those of the previously reported cases with monosomy for the middle portion of 2q.

A case with a terminal deletion of the long arm of chromosome 7

SummaryA malformed female infant with a de novo 7q terminal deletion (q32→qter) resulting from interchange between chromosome 4 and 7 was described. Her phenotype had a close resemblance to those of the previously reported cases. A further delineation of clinical features of 7q terminal deletion syndrome was attempted.