Chromosome Analysis Using Spectral Karyotyping (SKY)

Spectral karyotyping is a novel technique for chromosome analysis that has been developed based on the approach of the fluorescence in situ hybridization technique. Spectral karyotyping makes it feasible to diagnose a variety of diseases, because of its technology in painting each of the 24 human chromosomes with different colors. In recent years, it has become possible to adopt the usage of spectral karyotyping for research in general clinical practice, and its usability has attracted particular attention in the diagnosis of different diseases. In this review, we will explain the principle of the spectral karyotyping, as well as its specificity and limitation in detecting the genetic defects within clinical application by presenting two case reports

Novel c.2216T > C (p.I739T) Mutation in Exon 13 and c.1481T > A (p.L494X) Mutation in Exon 8 of MUT Gene in a Female with Methylmalonic Acidemia

We report herein a 1.5-year-old girl with methylmalonic acidemia (MMA) in whom two missense mutations were found: a novel I739T mutation located in exon 13 and the L494X mutation in exon 8. The results of organic acid test showed a pronounced increase in methylmalonate excretion with increased methylcitrate and 3-OH-propionate excretion, leading to a diagnosis of MMA, and Vitamin B12 administration was started. Analysis of the mut gene confirmed a T-to-A substitution at nucleotide position 1481 in exon 8 and a T-to-C substitution at nucleotide position 2216 in exon 13, leading to the amino acid isoleucine at position 739 being changed to threonine, resulting in c.2216T > C (p.I739T). The patient has now been on high-dose oral administration of Vitamin B12 and carnitine therapy (900 mg of levocarnitine chloride) for 5 years without experiencing further attacks, and her cognitive and motor development is normal. Further tests on residual enzyme activity, as well as experience with more cases, may shed light on the relationship between gene mutations and phenotypes in MMA

Clinically Mild form of Joubert Syndrome-related Disorder in a 7-year-old Female:A case report

Joubert syndrome-related disorders (JSRD) is a very rare syndrome observed with agenesis of the vermis,episodic hyperpnea, abnormal eye movements, and cerebellar ataxia and mental retardation. There have been many reports on the image-based diagnosis using MRI/CT, but not many clinical reports on the intelligence of subjects with JSRD. We herein report a clinically mild form of JSRD in a 7-year-old female. The patient did not have any clinical abnormalities in the neonatal period.She initially visited the neurology outpatient department at 6 months of age because her neck was still unstable. A brain MRI was conducted to assess symptoms of abnormal eye movements and body trunk cerebella rataxia, and she was diagnosed with JSRD based on the observation of agenesis of the vermis and characteristic molar tooth signs. Regarding her motor development, she was able to hold her head up at 7months of age, and was able to sit up at 1 year and 2 months old. She underwent rehabilitation, and a wide base cerebellar gait was observed when she was 5 years old. In addition, at 5 years of age, she could intermittently speak two-word sentences, draw pictures with an understanding of color, and was able to engage in actions such as throwing a ball. At 6 years of age, her conversation became better. She entered elementary school at 7 years of age, was able to go up and down stairs, read words, do single-digit addition, and write many Chinese characters with a pencil. The intellectual dysfunction of subjects with JSRD is generally moderate to severe. Thus, this case was diagnosed to be a clinically mild form of JSRD, because the patient exhibited limited effects on her intelligence

Structural basis of Sec-independent membrane protein insertion by YidC

[プレスリリース]バイオサイエンス研究科膜分子複合機能学研究室の塚崎智也准教授らの研究グループが、タンパク質を細胞膜に組み込むメカニズムを解明しました（2014/04/17）Newly synthesized membrane proteins must be accurately inserted into the membrane, folded and assembled for proper functioning. The protein YidC inserts its substrates into the membrane, thereby facilitating membrane protein assembly in bacteria; the homologous proteins Oxa1 and Alb3 have the same function in mitochondria and chloroplasts, respectively1, 2. In the bacterial cytoplasmic membrane, YidC functions as an independent insertase and a membrane chaperone in cooperation with the translocon SecYEG3, 4, 5. Here we present the crystal structure of YidC from Bacillus halodurans, at 2.4 Å resolution. The structure reveals a novel fold, in which five conserved transmembrane helices form a positively charged hydrophilic groove that is open towards both the lipid bilayer and the cytoplasm but closed on the extracellular side. Structure-based in vivo analyses reveal that a conserved arginine residue in the groove is important for the insertion of membrane proteins by YidC. We propose an insertion mechanism for single-spanning membrane proteins, in which the hydrophilic environment generated by the groove recruits the extracellular regions of substrates into the low-dielectric environment of the membrane

Better Prognosis in Newborns with Trisomy 13 Who Received Intensive Treatments: A Retrospective Study of 16 Patients

Intensive treatment for newborns with trisomy 13 is controversial because of their lethal prognosis. We report the better life prognosis of patients with trisomy 13 who received intensive treatment. At our hospital, we provided an intensive management to such patients including resuscitation and surgical procedures as required. Herein, we present the results of a retrospective study (1989–2010) of 16 trisomy 13 cases who received an intensive treatment. None was diagnosed to have trisomy 13 before birth; 9 were delivered by C-section and oxygen was administered to all patients during postpartum resuscitation. Mechanical ventilation was used in 9 patients after tracheal intubation and tracheotomy was performed in 2 patients when withdrawing of extubation was difficult. Regarding prognosis, 9 patients died, 3 were referred to another hospital, and 4 were discharged from the hospital. Four and 7 patients died within 7 and 30 days after birth, respectively. Nine patients survived for >1 month, 7 for >180 days, and 5 for >3 years. Median survival for 16 patients was 733 days. The patients who received intensive treatments survived longer compared to the previous data. This study provides useful information concerning genetic counseling, especially from an ethical point of view, before providing intensive management to newborns with trisomy 13

ショウニカ リョウイキ ニオケル ストレス・バロメーター ノ リンショウ オウヨウ : ショウニ ノ ストレス・バロメーター

精神的あるいは肉体的ストレスに対して.生体がどのように対応しているかをみる指標として,尿中の17-水酸化コルチコステロイド(17-OHCS)(生体の摩耗と断裂)と17-ケトステロイド硫酸抱合体(生体の修復と回復)とを同時に測定することによって把握できる,これらはストレス・バロメーターと呼ばれている.我々は世界で初めてこのストレス・バロメーターの小児の正常値を明らかにし,また小児科領域での各種疾患での臨床応用の可能性についても明らかにした.すなわち,夜尿症では精神的ストレスに関係する二次性夜尿症だけでなく,一次性夜尿症でもストレス・バロメーターが異常を示す症例では抗うつ剤の効果を認めた.また不登校は各種原因で起きるが,いじめが関与しているとストレス・バロメーターは異常を示す.原因が解決され,登校できるようになるとストレス・バロメーターは正常化する.神経性食欲不振症は思春期の女性に特有な疾患である,多くの症例では尿中17-OHCSは低下しているが,逆に高値を示す症例では学校でのいじめや家庭内でのトラブルが継続していることがある.痒みや痛みに対してもストレス・バロメーターは敏感に反応する.このようにストレス・バロメーターを測定することによって,問診ではわからなかったストレスの関与の仕方がわかり,臨床的にストレス・バロメーターを測定することは有用である

Anterior Spinal Artery Syndrome in 13-year Old boy:A Case Report

We herein report a rare case of a child patient with anterior spinal artery syndrome. The patient presentedwith mobility impairment in the lower limbs after suffering from a common cold. Temperature perceptionand pain perception were lost in both sides below the level of the fourth thoracic spine. In a thoracicspine MRI, abnormal signals were detected in the ventral side of the spinal cord below the Th3 level, thusleading to our diagnosis of anterior spinal artery syndrome. Gamma globulin therapy and steroid pulse therapywere applied concomitantly but no obvious effects were obtained. Continuing treatment with rehabilitationstarted for one month. Four months later, he was able to maintain a standing position and walk using awalking stick. The loss of temperature perception and pain perception in both sides below the Th4 remained.In the present case, movements in daily life became possible through the effects of rehabilitation. However,an impairment in the patient\u27s temperature and pain perception remained, and thus close attention is requiredfor various disorders and in daily life

Clinical features and subdural lesions in childhood onset Haemophilus influenzae meningitis

It becomes difficult to treat the onset of childhood Haemophilus influenza type b( Hib) meningitis due tothe appearance of b-lactamase negative ampicilin resistance( BLNAR). We investigated the clinical featuresof Hib meningitis with subdural lesions. From January 2000 to December 2006, we experienced 8 patientswith Hib meningitis. All patients were not inoculated with Hib vaccine. Five of them were onset under 1year old. Rapid latex diagnoses were made in 5 patients, among whom 4 patients showed Hib positive. Thegenotypes were determined in 4 patients with BLNAR. Combined with cefotaxime sodium (CTX) and ampicillin(ABPC) were used in 3 patients for the initial antibiotics, panipenem/betamipron( PAPM/BP) in 2,meropenem hydrate( MEPM) in 1, MEPM + ceftriaxone sodium( CTRX) in 1, and concomitant use of dexamethasonein 7 paitents. MRI showed subdural hygroma in 4 patients and subdural abscess in 4 patients.Subdural lesions appeared on Day 1 to Day 18 from the onset. Three patients with subdural abscess haveperformed subdural taps, and 2of them with difficulties after subdural taps were necessary to do oral administrationof chloramphenicol( CP).In our report, all of the patients developed subdural lesions. The development of subdural lesions cannotbe avoided with only the conventional antibiotics and dexamethasone therapy. Our cases suggested earliersubdural taps with oral administration of CP might be to improve both the general condition and control thesubdural lesions with Hib meningitis. Moreover, we should pay attention to the preventive vaccination ofHib

Lennox-Gastaut Syndrome Associated with Unilateral Hemispheric Porencephaly

We report an 18 year-old male with a hemispheric large porencephaly who demonstrated symptomaticWest syndrome and then developed into Lennox-Gastaut syndrome. An electroencephalogram showed anasymmetrical high voltage slow spike and wave discharges only on the right side as a side of porencephalichemisphere. Interestingly, on the opposite side of the porencephalic hemisphere, an electroencephalogramshowed a low amplitude background activity in general. In this unique features both right side hemisphericporencephaly and asymmetric high voltage slow spike and waves due to Lennox-Gastaut syndrome, theporencephalic hemisphere due to cortical parenchymal loss may be more affected than the other hemisphereby epileptiform discharge in this patient