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Takahito Wada

Publications and source records attributed to Takahito Wada.

9 recordsLinked to original sources
PubMed2006

A new detection method for ATRX gene mutations using a mismatch-specific endonuclease.

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X, OMIM 301040) is a syndromic form of X-linked mental retardation (XLMR). It is caused by a mutation in the ATRX gene, which is also involved in other syndromic forms of XLMR as well as in non-syndromic XLMR, both in males and in females. To analyze the full range of disease-causing mutations for genetic counseling and to establish phenotype-genotype correlations, we have established a new screening method for mutations in the ATRX gene, which uses mismatch-specific endonuclease. We applied this method to confirm 13 known mutations in our patients, some of which have been difficult to be demonstrated by conventional denaturing high-performance liquid chromatography. Furthermore, we found four additional mutations in four ATR-X patients whose clinical diagnosis had not been confirmed at the molecular level. In this method, experimental conditions do not need to be altered depending on mutation sites, and it should be the alternative method for mutation screening.

Base Pair Mismatch↗
PubMed2006

A novel splicing mutation of the ATRX gene in ATR-X syndrome.

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X, MIM#301040) is an X-linked recessive condition affecting males. ATR-X is characterized by severe mental retardation, mild HbH disease, dysmorphic facies, and genital and skeletal abnormalities. ATR-X is caused by mutations in the ATRX gene. Most mutations affect two functionally important domains, the ADD domain and the helicase domain. Here, we report on two brothers with the ATR-X phenotype without HbH disease; both had a mutation in the 5' upstream region of the ADD domain of the ATRX gene. This mutation was a G to T nucleotide substitution at the 3' end of exon 5 and resulted in splicing out of exons 5 and 6. Analysis of cDNA structure may clarify genotype-phenotype correlations in ATR-X because splicing mutation could be detectable only by cDNA analysis.

Adolescent↗
PubMed2005

Non-skewed X-inactivation may cause mental retardation in a female carrier of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X): X-inactivation study of nine female carriers of ATR-X.

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X) is a syndromic form of X-linked mental retardation. We investigated the X-inactivation status of nine female ATR-X carriers by methylation-specific PCR of the HUMARA gene. Six carriers demonstrated a skewed X-inactivation pattern (>90:10) and one showed a non-skewed pattern (72:28), while two were uninformative because of homozygosity for the CAG repeat polymorphic alleles in the HUMARA. Only the carrier mother who showed non-skewed X-inactivation had moderate mental retardation. These findings suggest that mutations in ATRX may cause mental retardation in females, if the X chromosome carrying mutated ATRX is not properly inactivated.

Chromosomes, Human, X↗
PubMed2005

A woman with 46,XX,dup(16)(p13.11 p13.3) and the ATR-X phenotype.

We report a Japanese woman with 46,XX,dup(16)(p13.11p13.3), who closely resembled the phenotype of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X, MIM # 301040). Although she never had alpha-thalassemia, she showed characteristic clinical features including severe mental retardation, characteristic facies and behavior. ATR-X is caused by mutations of the ATRX gene. Although the function of ATRX protein has remained unclarified, it is thought to be involved in the regulation of several genes. The only target gene identified so far is the alpha-globin gene at 16p13.3. Clinical similarity among patients with ATR-X and dup(16)(p13.11p13) may indicate that some target genes regulated by ATRX reside in the duplicated region between 16p13.11 and 16p13.3, and that these genes are abnormally upregulated in ATR-X differently from the alpha-globin gene.

Adult↗
PubMed2005

Uniparental disomy and imprinting defects in Japanese patients with Angelman syndrome.

We examined 54 patients with deletion-negative Angelman syndrome (AS) using DNA methylation testing and microsatellite polymorphism analysis, and identified three patients with paternal uniparental disomy (UPD) and seven patients with imprinting defects (ID). The three patients with UPD were shown to have paternal isodisomy 15, which we hypothesized to have arisen from duplication of chromosome 15. Two of the patients with ID were siblings and carried microdeletions of the imprinting center (IC), while the remaining five patients had no evidence of deletions and represented sporadic cases. Two of the three patients with UPD and two of the seven patients with ID had not developed seizures. The only patients displaying microcephaly were those with ID who had microdeletions at the IC. These data support the previous findings that indicate that patients with UPD and ID may have a milder phenotype of AS.

Angelman Syndrome↗
PubMed2003

A novel P gene missense mutation in a Japanese patient with oculocutaneous albinism type II (OCA2).

BACKGROUND: Oculocutaneous albinism type II (OCA2) is an autosomal recessively inherited disorder, characterized by white hair and skin, and loss of pigment in the eyes. Mutations in P gene have been shown to result in OCA2. So far, two cases have been reported from Japan. OBJECTIVE: We had an opportunity to examine a case of albinism, and screened the mutations of tyrosinase and P gene. METHODS: Genomic DNA was prepared from peripheral leukocytes. All of the exons and flanking introns of tyrosinase and P gene were PCR-direct-sequenced. RESULTS: Although no mutations were found in tyrosinase, we found two missense substitutions, A481T and Q799H in P gene. The A481T has previously been shown to result in partial function of the P protein. CONCLUSION: The Q799H mutation is not a common polymorphism among normal Japanese, seems most likely to be a pathological OCA2 mutation among Japanese with this form of albinism.

Albinism, Oculocutaneous↗
PubMed2002

Germline mosaicism of a novel mutation in lysosome-associated membrane protein-2 deficiency (Danon disease).

We identified a family with lysosome-associated membrane protein-2 deficiency (Danon disease) associated with a novel 883 ins-T mutation in the lysosome-associated membrane protein-2 gene located at Xq24. Although the affected son and daughter carried the same mutation, it was not detected in their mother's peripheral blood or buccal cells; this indicated germline mosaicism. This is the first molecular evidence for germline mosaicism in Danon disease and has important implications for genetic counseling.

Adult↗
PubMed2002

Wide clinical variability in a family with a CACNA1A T666m mutation: hemiplegic migraine, coma, and progressive ataxia.

We report a Japanese family carrying a T666M missense mutation of CACNA1A. Affected members demonstrated a strikingly wide clinical spectrum including migraine, hemiplegia, coma, and progressive cerebellar ataxia. Despite such variability of the clinical features, they demonstrated similar magnetic resonance imaging findings demonstrating cerebellar atrophy predominantly of the cerebellar vermis. These magnetic resonance images appeared not to correlate with clinical severity. Our findings should indicate that a T666M mutation of CACNA1A may be associated with more variable clinical features and that paroxysmal hemiplegic migraine attacks and progressive cerebellar atrophy should have distinct mechanisms of pathogenesis.

Adult↗