Takashi Ishii

Random X‐inactivation in a girl with duplication Xp11.21–p21.3: Report of a patient and review of the literature

We describe a 10-month-old girl with abnormal clinical findings and Xp duplication. She showed poor weight gain and developmental retardation, and had several minor anomalies including pigmentary dysplasia (hypomelanosis of Ito). She had a partial short arm duplication in the paternally derived X chromosome, 46,X,dup(X)(p11. 21p21.3), with the normal and duplicated X chromosomes randomly inactivated. These findings indicate that gross functional imbalance in the cells with an active dup(X) chromosome has caused global developmental defects in the patient, and that functional chromosomal mosaicism with respect to the duplicated Xp region has resulted in pigmentary dysplasia. Literature review of 52 patients with partial X duplications revealed (1) random or skewed but not completely selective X-inactivation in 9 of 45 patients examined for the X-inactivation pattern, independently of the size or location of duplicated segments, (2) apparently normal phenotype in 6 of 9 patients with random or skewed X-inactivation, and (3) an abnormal phenotype in 13 of 35 patients with completely selective inactivation of dup(X) chromosomes.

Microphthalmia with linear skin defects syndrome in a mosaic female infant with monosomy for the Xp22 region: molecular analysis of the Xp22 breakpoint and the X-inactivation pattern

This paper describes a female infant with microphthalmia with linear skin defects syndrome (MLS) and monosomy for the Xp22 region. Her clinical features included right microphthalmia and sclerocornea, left corneal opacity, linear red rash and scar-like skin lesion on the nose and cheeks, and absence of the corpus callosum. Cytogenetic studies revealed a 45,X[18]/46,X,r(X)(p22q21) [24]/46,X,del(X)(p22)[58] karyotype. Fluorescence in situ hybridization analysis showed that the ring X chromosome was positive for DXZ1 and XIST and negative for the Xp and Xq telomeric regions, whereas the deleted X chromosome was positive for DXZ1, XIST, and the Xq telomeric region and negative for the Xp telomeric region. Microsatellite analysis for 19 loci at the X-differential region of Xp22 disclosed monosomy for Xp22 involving the critical region for the MLS gene, with the breakpoint between DXS1053 and DXS418. X-inactivation analysis for the methylation status of the PGK gene indicated the presence of inactive normal X chromosomes. The Xp22 deletion of our patient is the largest in MLS patients with molecularly defined Xp22 monosomy. Nevertheless, the result of X-inactivation analysis implies that the normal X chromosomes in the 46,X,del(X)(p22) cell lineage were more or less subject to X-inactivation, because normal X chromosomes in the 45,X and 46,X,r(X)(p22q21) cell lineages are unlikely to undergo X-inactivation. This supports the notion that functional absence of the MLS gene caused by inactivation of the normal X chromosome plays a pivotal role in the development of MLS in patients with Xp22 monosomy.

Large fontanelles are a shared feature of haploinsufficiency of RUNX2 and its co-activator CBFB.

ABSTRACT CBFB at 16q22 heterodimerizes with either RUNX2 (also known as CBFA1) or RUNX1 (CBFA2) to activate the transcription of downstream molecules. RUNX2 regulates osteoblast differentiation and chondrocyte maturation and its haploinsufficiency leads to cleidocranial dysplasia, characterized large fontanelles, hypoplasia or aplasia of the clavicles, hypoplasia of the distal phalanges, and a wide pubic symphysis. Complete loss of Runx1 or Cbfb in mice is lethal because of the absence of fetal liver hematopoiesis. Fetal rescue in Cbfb–/– mice by providing the Cbfb functions in the hematopoietic progenitors leads to wide fontanelle and delayed chondrocyte maturation, presumably resulting from the incomplete function of the transcriptional pathway mediated by the Cbfb‐Runx2 heterodimer. The present report describes a patient with a small deletion of chromosome 16q22.1 encompassing CBFB. Skeletal abnormalities included a widely open fontanelle, multiple wormian bones along the sagittal suture, hypoplasia of the distal phalanges, and mildly shortened clavicles. G‐banding analysis revealed a shortening of the 16q22.1 band. A fluorescence in situ hybridization analysis, using the BAC probe spanning the CBFB locus at 16q22.1, revealed that the CBFB probe hybridized to only one of the two homologous chromosome 16 regions. Array‐comparative genomic hybridization analysis revealed that the deletion spans 1.2 megabases. In reviewing eight previously reported cases of 16q interstitial deletions involving band q22, large cranial sutures were noted in all but one case. Considering the phenotypic similarity of the 16q22 deletion case and Cbfb–/– mice rescued for hematopoiesis and the consistency of the phenotype among 16q22 deletion cases, we suggest that the common phenotypic feature of the 16q22 deletion, large fontanelles, can be attributed to a haploinsufficiency of CBFB.

Influence of Temperature on the Structure and Properties of an Anodized Native GaAs Oxide

The influence of temperature on the properties, the composition and the structure of the anodically grown native GaAs oxide is investigated. The oxide is very stable below 350°C. Above 350°C, the oxide begins to decompose first by releasing water. The oxide decomposes most rapidly around 450°C mainly by vaporizing water and arsenic monoxide. By decomposition, drastic changes of oxide properties and composition are observed. The oxide decomposition is completed at 700°C resulting in pure gallium oxide. By coating SiO2 film on top of the anodized oxide film, GaAs is possible to be heat-treated at 800°C for 2 hours without any degradation of the GaAs surface.

High Power, High Reliability p-n Junction GaAs IMPATT Diodes for J-Band

p-n junction GaAs IMPATT diodes with Hi-Lo structure were studied for high output power, high efficiency and high reliability. High output power over 10 W was obtained with average efficiency of 20% with good yield by optimizing the carrier profile and investigating multi-chips operation. The maximum output power and efficiency were 11 W at 5.7 GHz and 23.3% at 6.5 GHz, respectively. Median failure time over 106 h at 200°C was deduced by an activation energy of 1.85 eV in diodes metallized with Au–Ge by accelerated life tests.

Flip-Chip Mounted GaAs Power FET with Improved Performances in X to Ku Band

A GaAs power field effect transistor with a new structure has been developed, in which source inductances and thermal resistance are remarkably reduced. In the structure, the chip with metal posts plated on the source, drain and gate pads is directly connected to the corresponding bonding area of a package by thermocompression bonding with no wire. Best results obtained are 2.5 W at 15 GHz, 4.1 W at 12 GHz and 6.0 W at 10 GHz. A power added efficiency as high as 27% is obtained in a 2400 µm device at 12 GHz.

High Performance Ni-Pd/GaAs Schottky Barrier Diodes Made by Electroplating

For fabricating high cutoff and high reliability GaAs Schottky barrier diodes, a method forming Schottky barrier by electroplating a Ni-Pd binary alloy on GaAs has been developed. This process enables to form Schottky barrier without stray capacitance due to overlay and without increase of series resistance due to oxidation and contamination of the GaAs surface. A high cutoff frequency more than 2000 GHz was realized. The Ni-Pd/GaAs Schottky barrier is stable and MTTF of 7.5×107 hours has been deduced at 60°C. Using these Schottky barrier diodes for a mixer in a SHF down-converter, conversion loss as low as 3.0 dB and system noise figure as low as 4.3 dB have been obtained with a 200 MHz band width at 12 GHz.