A novel HYLS1 homozygous mutation in living siblings with Joubert syndrome.

The p.Asp211Gly homozygous HYLS1 mutation is so far known to cause only hydrolethalus syndrome, a lethal malformation syndrome. We report living sibling patients with a homozygous no-stop mutation in exon 4 of HYLS1, NM_145014.2:c.900A>C (p.Ter300TyrextTer11) in the second decade of life. The proband has Joubert syndrome (JS). The younger brother also has JS and an enlarged posterior fossa that was initially diagnosed as Dandy-Walker malformation. The present mutation is unique as it affects the stop codon. The product protein HYLS1 plays an essential role in the formation of the primary cilium. This report provides insight into the spectrum of disorders involving midline brain defects closely related to cilium dysfunction or ciliopathy.

Homozygous c.14576G>A variant of RNF213 predicts early-onset and severe form of moyamoya disease.

OBJECTIVE: RNF213 was recently reported as a susceptibility gene for moyamoya disease (MMD). Our aim was to clarify the correlation between the RNF213 genotype and MMD phenotype. METHODS: The entire coding region of the RNF213 gene was sequenced in 204 patients with MMD, and corresponding variants were checked in 62 pairs of parents, 13 mothers and 4 fathers of the patients, and 283 normal controls. Clinical information was collected. Genotype-phenotype correlations were statistically analyzed. RESULTS: The c.14576G>A variant was identified in 95.1% of patients with familial MMD, 79.2% of patients with sporadic MMD, and 1.8% of controls, thus confirming its association with MMD, with an odds ratio of 259 and p < 0.001 for either heterozygotes or homozygotes. Homozygous c.14576G>A was observed in 15 patients but not in the controls and unaffected parents. The incidence rate for homozygotes was calculated to be >78%. Homozygotes had a significantly earlier age at onset compared with heterozygotes or wild types (median age at onset 3, 7, and 8 years, respectively). Of homozygotes, 60% were diagnosed with MMD before age 4, and all had infarctions as the first symptom. Infarctions at initial presentation and involvement of posterior cerebral arteries, both known as poor prognostic factors for MMD, were of significantly higher frequency in homozygotes than in heterozygotes and wild types. Variants other than c.14576G>A were not associated with clinical phenotypes. CONCLUSIONS: The homozygous c.14576G>A variant in RNF213 could be a good DNA biomarker for predicting the severe type of MMD, for which early medical/surgical intervention is recommended, and may provide a better monitoring and prevention strategy.

SCN1B is not related to benign partial epilepsy in infancy or convulsions with gastroenteritis.

We hypothesized that benign partial epilepsy in infancy (BPEI) and convulsions with gastroenteritis (CwG) may have a similar genetic background, because previous studies indicate that clinical features overlap between BPEI and CwG. As carbamazepine is effective for cessation of clustering seizures in children with BPEI and CwG, some genetic mutations regarding sodium channels may be related to the development of BPEI and/or CwG. We focused on SCN1B encoding the voltage-dependent sodium channel ß subunit. We explored SCN1B mutation in 6 children with BPEI and 6 children with CwG. Genomic DNAs were extracted from peripheral blood samples accumulated from the patients and all 5 exons of SCN1B were amplified by standard PCR amplification. There were no SCN1B mutations or pathological single nucleotide polymorphisms in any of the patients, although the phenotypes of our patients were typical for BPEI or CwG. Our study demonstrated that SCN1B may not be related to the occurrence of BPEI or CwG.

Clinical features of microdeletion 9q22.3 (pat).

Congenital anomaly syndromes manifesting overgrowth are rare, and only a small number of recognized or defined conditions are known to be associated with overgrowth. Some of them are related to genomic imprinting as a genetic cause. We report a girl who showed pre- and postnatal overgrowth who was found to have a 2.3-Mb deletion of 9q22.32 involving PTCH1, the gene responsible for Gorlin syndrome (nevoid basal cell carcinoma syndrome), by array-comparative genomic hybridization analysis. Clinical re-evaluation according to the diagnostic criteria was performed after identification of the PTCH1 deletion, and the patient was then diagnosed as having Gorlin syndrome. Further delineation involved unusual features including cerebellar dysplasia, an ectopic meninx on her shoulder, and an intraorbital hemangioma. Overgrowth is not a common finding in Gorlin syndrome. We reviewed 23 patients reported to have a 9q22 deletion. Five patients, including our patient, had overgrowth and loss of the paternal allele.

Processing and mechanical properties of autogenous titanium implant materials.

Pure titanium and some of its alloys are currently considered as the most attractive metallic materials for biomedical applications due to their excellent mechanical properties, corrosion resistance, and biocompatibility. It has been demonstrated that titanium and titanium alloys are well accepted by human tissues as compared to other metals such as SUS316L stainless steel and Co-Cr-Mo type alloy. In the present study, highly porous titanium foams with porosities

Heterogeneous expression of nm23 gene product as a predictor of lymph nodal status in human breast cancer.

The nm23 gene was originally identified by differential hybridization of metastatic murine melanoma cell lines. Some experimental studies demonstrated a significantly low metastatic potential of melanoma cell lines transfected with the nm23 gene. In this study, we clarified the relationship between intracellular nm23-immunoreactivity and lymph nodal status of human breast cancer. We analyzed 82 surgically removed breast tumors including 67 invasive carcinomas (ductal, lobular and mucinous carcinomas). The nm23 expression was diffusely positive in the benign tumors and non-invasive carcinomas. Of the invasive ductal carcinomas, lymph node metastasis was found in 67.7% (21/31) of the focally positive/negative cases and in 18.2% (4/22) of the diffusely positive cases (p<0.001). Immunohistochemically, advanced margins of invasive carcinomas with lymph node metastasis were shown to be negative for nm23 expression, while intraductal carcinoma components were positive. This observation suggested that focally positive/negative nm23 expression can be a predictor of lymph node metastasis of invasive ductal breast carcinoma.

Age differences of psychiatric inpatients presenting with physical complications.

We reviewed the records of 292 inpatients in the psychiatric ward of Kagoshima University Hospital who were referred from other medical facilities over a 5-year period in order to clarify age differences in the reason for referral. Patients were classified into groups of physically and mentally ill individuals based on indications for admission. Both groups were further divided into four subgroups based on age. The incidence of inpatients with physical illnesses increased with age. Conditions related to pregnancy, childbirth and the puerperium occurred at high frequency in female patients in the 20- to 39-year-old subgroup. Individuals in the 40- to 59-year-old and in the > or = 60 years subgroups suffered more frequently from neoplasms. The proportion of patients manifesting a defective state in all age subgroups with the exception of the under 19-year-old subgroup was significantly higher in the physical illness group than in the mental illness group. The proportion of patients in a depressive state in the > or = 60 years subgroup was significantly higher in the mental illness group than in the physical illness group. Hence, it is necessary to find a method to be able to cope with psychiatric patients with physical complications to solve this problem.