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Biomedical subjects

Kenji Kurosawa

Publications and source records attributed to Kenji Kurosawa.

At least 37 records · Page 2Linked to original sources
PubMed2005

Epilepsy and neurological findings in 11 individuals with 1p36 deletion syndrome.

The 1p36 deletion syndrome is a newly delineated multiple congenital anomalies/mental retardation syndrome characterized by mental retardation, growth delay, epilepsy, congenital heart defects, characteristic facial appearance, and precocious puberty. We analyzed 11 patients by fluorescence in situ hybridization (FISH) using commercially available bacterial artificial chromosome and P1-derived artificial chromosome genomic clones to define the chromosomal deletion responsible for the 1p36 deletion syndrome. Cytogenetic investigation revealed two cases with a terminal deletion of 1p36. Nine patients had an apparently normal karyotype with standard G-bands by trypsin using Giemsa (GTG), but FISH screening with the highly polymorphic genetic marker D1Z2, which is mapped to 1p36.3 and contains an unusual reiterated 40-bp variable number tandem repeat, revealed a submicroscopic deletion. All patients had severe to profound mental retardation. Based on the University of California Santa Cruz Genome Browser, we constructed a deletion map and analyzed the relationship between neurological findings and chromosomal deletions for the 11 cases. Six cases had intractable epilepsy and three had no seizures. The common deletion interval was about 1 million base pairs (Mbp) located between RP11-82D16 and RP4-785P20 (Rho guanine exchange factor (GEF) 16). The severity of clinical symptoms correlates with the size of the deletion. This is demonstrated by the 3 patients with at least 8Mbp deletions that display profound mental retardation and congenital heart defects. Although haploinsufficiency of the potassium channel beta-subunit (KCNAB2) is thought to be responsible for intractable seizures in the 1p36 deletion syndrome, this was not the case for 3 of the 11 patients in this study. Further investigation of the 1p36 region is necessary to allow identification of genes responsible for the 1p36 deletion syndrome.

Abnormalities, Multiple↗
PubMed2005

Joint angle control by FES using a feedback error learning controller.

The feedback error learning (FEL) scheme was studied for a functional electrical stimulation (FES) controller. This FEL controller was a hybrid regulator with a feedforward and a feedback controller. The feedforward controller learned the inverse dynamics of a controlled object from feedback controller outputs while control. A four-layered neural network and the proportional-integral-derivative (PID) controller were used for each controller. The palmar/dorsi-flexion angle of the wrist was controlled in both computer simulation and FES experiments. Some controller parameters, such as the learning speed coefficient and the number of neurons, were determined in simulation using an artificial forward model of the wrist. The forward model was prepared by using a neural network that can imitate responses of subject's wrist to electrical stimulation. Then, six able-bodied subjects' wrist was controlled with the FEL controller by delivering stimuli to one antagonistic muscle pair. Results showed that the FEL controller functioned as expected and performed better than the conventional PID controller adjusted by the Chien, Hrones and Reswick method for a fast movement with the cycle period of 2 s, resulting in decrease of the average tracking error and shortened delay in the response. Furthermore, learning iteration was shortened if the feedforward controller had been trained in advance with the artificial forward model.

Artificial Intelligence↗
PubMed2005

Comprehensive screening of CREB-binding protein gene mutations among patients with Rubinstein-Taybi syndrome using denaturing high-performance liquid chromatography.

Mutations in the CREBBP (CREB-binding protein gene) cause Rubinstein-Taybi syndrome (RSTS). At present, however, genetic testing of CREBBP is not commonly applied in clinical settings because the currently available assays are technically and financially demanding, mainly because of the size of the gene. In the present study, we took advantage of a highly sensitive and specific, automated denaturing high-performance liquid chromatography (DHPLC) technique. First, we developed a DHPLC-based protocol to analyze the entire coding region of CREBBP. Second, we analyzed genetic samples from 21 RSTS patients using DHPLC. The coding region was amplified by 41 primer pairs, all of which have the same cycling conditions, aliquoted on a 96-well format PCR plate. In this manner, all the exons were simultaneously amplified using a single block in a PCR machine. We then wrote a computer script to analyze all the PCR amplicons generated from various portions of the CREBBP gene in a serial manner at optimized conditions determined individually for each amplicon. Heterozygous CREBBP mutations were identified in 12 of the 21 patients: five frameshift mutations, three nonsense mutations, two splice-site mutations, and two missense mutations. The resulting detection rate of 57% was comparable to the outcome of previous studies. The relatively high detection rate in the present study demonstrates the enhanced sensitivity of the DHPLC-based mutation analysis, as exemplified by mutation analyses of other genes. The implementation of similar methodologies for other dysmorphic syndromes will help medical geneticists to confirm their clinical impressions and to provide accurate genetic counseling for patients and their families.

CREB-Binding Protein↗
PubMed2004

Girl with monosomy 1p36 and Angelman syndrome due to unbalanced der(1) transmission of a maternal translocation t(1;15)(p36.3;q13.1).

We report on a girl with monosomy 1p36.3 and Angelman syndrome due to an unbalanced transmission of a maternal balanced chromosomal translocation. She manifested monosomy 1p36 and Angelman syndrome including generalized hypopigmentation, ataxic movements, intractable seizures with characteristic electroencephalographic (EEG) abnormality compatible with Angelman syndrome, and other minor anomalies, large anterior fontanelle, severe psychomotor retardation, and seizures due to monosomy 1p36. Her karyotype was 45, XX, der(1) t(1;15)(p36.31;q13.1),-15, derived from maternal translocation. Molecular analysis determined a breakpoint of 1p between D1S243 and D1S468, which suggested that most genes contributing to the common phenotype are in the distal region.

Abnormalities, Multiple↗
PubMed2004

Molecular characterization of inv dup del(8p): analysis of five cases.

We analyzed five patients with inverted duplication deletion of 8p [inv dup del(8p)] using fluorescence in situ hybridization (FISH) and short tandem repeat polymorphism (STRP) analysis. In all patients, inv dup del(8p) consisted of a deleted distal segment, an intact in-between segment, and a duplicated proximal segment. In all of them, the proximal breakpoint of the deletion and one of the breakpoints of the duplication were identical, each located at one of the two olfactory receptor gene clusters at 8p23. FISH analysis showed all their mothers to be heterozygous carriers of an 8p23 inversion [inv(8)(p23)]. STRP analysis indicated that the deletions occurred in maternally derived chromosomes. The duplicated segments had two copies of maternal, either heterozygous or homozygous alleles. These findings support and reinforce those in 16 patients with inv dup del(8p) and their parents by Floridia et al. [1996: Am J Hum Genet 58:785-796] and subsequent additional studies of 10 of them by Giglio et al. [2001: Am J Hum Genet 68:874-883]. Based on these findings, we propose a model for the inv dup del(8p) formation. The inverted segment and its normal counterpart in inv(8)(p23) heterozygous carrier mothers form a loop at the pachytene period of meiosis I. Inv dup del(8p) with heterozygous duplication is formed through at least one meiotic recombination within the loop. Inv dup del(8p) with the homozygous duplication arises through two meiotic recombinations on the inv(8)(p23) chromosome (one within the loop and the other between the loop and centromere). Subsequent rescue by eliminating a part of the duplicated segment and a centromere enables formation of viable inv dup del(8p). The frequency of the inv(8)(p23) allele is 39% in a normal Japanese population, comparable to 26% in Europeans Giglio et al. [2001: Am J Hum Genet 68:874-883]. The proposed mechanism of formation of inv dup del(8p) requires two independent events (a recombination within the loop and subsequent rescue), which may explain its rarity.

Abnormalities, Multiple↗
PubMed2003

Preferential paternal origin of microdeletions caused by prezygotic chromosome or chromatid rearrangements in Sotos syndrome.

Sotos syndrome (SoS) is characterized by pre- and postnatal overgrowth with advanced bone age; a dysmorphic face with macrocephaly and pointed chin; large hands and feet; mental retardation; and possible susceptibility to tumors. It has been shown that the major cause of SoS is haploinsufficiency of the NSD1 gene at 5q35, because the majority of patients had either a common microdeletion including NSD1 or a truncated type of point mutation in NSD1. In the present study, we traced the parental origin of the microdeletions in 26 patients with SoS by the use of 16 microsatellite markers at or flanking the commonly deleted region. Deletions in 18 of the 20 informative cases occurred in the paternally derived chromosome 5, whereas those in the maternally derived chromosome were found in only two cases. Haplotyping analysis of the marker loci revealed that the paternal deletion in five of seven informative cases and the maternal deletion in one case arose through an intrachromosomal rearrangement, and two other cases of the paternal deletion involved an interchromosomal event, suggesting that the common microdeletion observed in SoS did not occur through a uniform mechanism but preferentially arose prezygotically.

Abnormalities, Multiple↗
PubMed2003

Further delineation of the behavioral and neurologic features in Costello syndrome.

To describe clinical and neurodevelopmental phenotypes of Costello syndrome, we performed a retrospective review of the clinical records and findings in 10 children with Costello syndrome. All patients showed significant postnatal growth retardation and severe feeding difficulties leading to failure to thrive from early infancy. All required tube feeding and some needed high-calorie formulas for variable periods. Developmental quotients/IQs in seven children were 50 or less, and three were in the mildly retarded range. Five had seizures. Remarkable manifestations not previously reported were the characteristic behavior in infancy. Although happy and sociable personality was always emphasized in the genetic literature, all children showed significant irritability, including hypersensitivity to sound and tactile stimuli, sleep disturbance, and excess shyness with strangers in infancy. Those symptoms usually disappeared around age 2-4 years. Other clinical signs included cardiac abnormalities (8), musculoskeletal abnormalities (10), ophthalmological manifestations (5), increased urinary vanillymandelic acid (VMA) and homovanillic acid (HVA) (3), rhabdomyosarcoma (1), laryngomalacia (1), and cryptorchidism (1). Only three girls had papillomata. Family histories were negative for Costello syndrome. In conclusion, we confirm the wide spectrum of mental function in patients with Costello syndrome, which ranges from severe to mild. During infancy Costello syndrome showed remarkable irritability with severe feeding problems, which attributes significant difficulties to the parents of affected children.

Abnormalities, Multiple↗
PubMed2003

Fifty microdeletions among 112 cases of Sotos syndrome: low copy repeats possibly mediate the common deletion.

Sotos syndrome (SoS) is an autosomal dominant overgrowth syndrome with characteristic craniofacial dysmorphic features and various degrees of mental retardation. We previously showed that haploinsufficiency of the NSD1 gene is the major cause of SoS, and submicroscopic deletions at 5q35, including NSD1, were found in about a half (20/42) of our patients examined. Since the first report, an additional 70 SoS cases consisting of 53 Japanese and 17 non-Japanese have been analyzed. We found 50 microdeletions (45%) and 16 point mutations (14%) among all the 112 cases. A large difference in the frequency of microdeletions between Japanese and non-Japanese patients was noted: 49 (52%) of the 95 Japanese patients and only one (6%) of the 17 non-Japanese had microdeletions. A sequence-based physical map was constructed to characterize the microdeletions. Most of the microdeletions were confirmed to be identical by FISH analysis. We identified highly homologous sequences, i.e., possible low copy repeats (LCRs), in regions flanking proximal and distal breakpoints of the common deletion, This suggests that LCRs may mediate the deletion. Such LCRs seem to be present in different populations. Thus the different frequency of microdeletions between Japanese and non-Japanese cases in our study may have been caused by patient-selection bias.

Carrier Proteins↗
PubMed2002

Paternal UPD14 is responsible for a distinctive malformation complex.

We present a boy and two girls with paternal uniparental disomy of chromosome 14q (patUPD14). One girl had a Robertsonian translocation, whereas two a normal karyotype. Based on the manifestations of these patients and four previously reported patients who all had translocated chromosome 14, The patUPD14 was thought to constitute a distinctive syndrome. The hallmarks included abdominal muscular defects, skeletal anomalies, and characteristic facies. The phenotype of patUPD14 was consistent with that of a previously reported mouse model, i.e., mouse embryos with paternal uniparental disomy of chromosome 12 that has a region orthologous to that of human chromosome 14. Dose effects of newly recognized imprinted genes on human chromosome 14q32, DLK1 and GTL2, could play an important role in the pathogenic mechanism of the distinctive malformation complex.

Abnormalities, Multiple↗
PubMed2002

Patellar dislocation in Kabuki syndrome.

We describe four individuals (two females and two males) with Kabuki syndrome and recurrent dislocation of the patella. The age of diagnosis of patellar dislocation ranged from 11 to 23 years. One individual underwent excision of the free fragment and transfer of the tibial tuberosity with good outcome. Two required patellar brace for instability. Characteristics of individuals with the syndrome at a high risk of patellar dislocation include female, adolescence or young adulthood, joint laxity, and obesity.

Abnormalities, Multiple↗
PubMed2002

Sotos syndrome associated with a de novo balanced reciprocal translocation t(5;8)(q35;q24.1).

We describe a de novo balanced reciprocal translocation between the long arms of chromosomes 5 and 8 [46,XX,t(5;8)(q35;q24.1)] in a 15-month-old girl with a typical Sotos syndrome phenotype. Involvement of the 5q35 region was previously reported (Maroun et al. [1994: Am J Med Genet 50:291-293]) as one of translocation breakpoints in the present patient. We suggest that the gene responsible for Sotos syndrome is located to a distal long-arm region of chromosome 5.

Chromosomes, Human, Pair 5↗
PubMed2002

A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy.

Chromosome 1p36 deletion syndrome is characterized by hypotonia, moderate to severe developmental and growth retardation, and characteristic craniofacial dysmorphism. Muscle hypotonia and delayed motor development are almost constant features of the syndrome. We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association may indicate that one of the CFTD loci is located at 1p36. Ski proto-oncogene -/- mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome. Because fluorescent in situ hybridization analysis revealed that the human SKI gene is deleted in our patient, some genes in 1p36, including SKI proto-oncogene, may be involved in muscle hypotonia and delayed motor development in this syndrome.

Animals↗