A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third patient with Takenouchi-Kosaki syndrome.

Takenouchi-Kosaki syndrome (TKS) is a congenital malformation syndrome characterized by severe developmental delay, macrothrombocytopenia, camptodactyly, sensorineural hearing loss, and dysmorphic facial features. Recently, a heterozygous de novo mutation (p.Tyr64Cys) in the CDC42 gene, which encodes a key small GTP-binding protein of the Rho-subfamily, was identified in two unrelated patients with TKS.

Maternally derived 15q11.2-q13.1 duplication and H19-DMR hypomethylation in a patient with Silver-Russell syndrome.

Silver-Russell syndrome (SRS) is a congenital developmental disorder characterized by intrauterine and postnatal growth failure, craniofacial features (including a triangular shaped face and broad forehead), relative macrocephaly, protruding forehead, body asymmetry and feeding difficulties. Hypomethylation of the H19 differentially methylated region (DMR) on chromosome 11p15.5 is the most common cause of the SRS phenotype.

Identification of a novel heterozygous mutation of the Aggrecan gene in a family with idiopathic short stature and multiple intervertebral disc herniation.

Aggrecan is a critical proteoglycan component of the extracellular matrix of the growth plates and articular cartilage and has a key role in the biophysical and biomechanical properties of cartilage. Recently, heterozygous mutations in the ACAN gene, which encodes aggrecan, have been identified in patients with short stature and accelerated bone age. We herein report another family with a heterozygous ACAN mutation associated with idiopathic short stature along with accelerated bone age and early-onset herniation of the lumbar discs at the levels of L1/2 through L5/S1.

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry.

Background: Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis.

Methods: This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II.

Genetic background of hyperphenylalaninemia in Nagasaki, Japan.

Phenylketonuria (PKU) and related hyperphenylalaninemia (HPA) are caused by a deficiency in hepatic phenylalanine hydroxylase (PAH). The incidence of PKU in Nagasaki prefecture is higher than that in all parts of Japan (1/15 894 vs 1/120 000). To investigate the genetic background of patients with HPA in Nagasaki prefecture, mutation analysis was done in 14 patients with PKU or mild HPA.

Reconstituted human myosin light chain phosphatase reveals distinct roles of two inhibitory phosphorylation sites of the regulatory subunit, MYPT1.

The myosin light chain phosphatase (MLCP) is a cytoskeleton-associated protein phosphatase-1 (PP1) holoenzyme and a RhoA/ROCK effector, regulating cytoskeletal reorganization. ROCK-induced phosphorylation of the MLCP regulatory subunit (MYPT1) at two sites, Thr696 and Thr853, suppresses the activity, although little is known about the difference in the role. Here, we developed a new method for the preparation of the recombinant human MLCP complex and determined the molecular and cellular basis of inhibitory phosphorylation.

SLC25A13 gene analysis in citrin deficiency: sixteen novel mutations in East Asian patients, and the mutation distribution in a large pediatric cohort in China.

Background: The human SLC25A13 gene encodes citrin, the liver-type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenotypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). The analyses of SLC25A13 gene and its protein/mRNA products remain reliable tools for the definitive diagnoses of CD patients, and so far, the SLC25A13 mutation spectrum in Chinese CD patients has not been well-characterized yet.

Methods And Results: By means of direct DNA sequencing, cDNA cloning and SNP analyses, 16 novel pathogenic mutations, including 9 missense, 4 nonsense, 1 splice-site, 1 deletion and 1 large transposal insertion IVS4ins6kb (GenBank accession number KF425758), were identified in CTLN2 or NICCD patients from China, Japan and Malaysia, respectively, making the SLC25A13 variations worldwide reach the total number of 81.

Pancreatic head resection preserving the main pancreatic duct for congenital hyperinsulinism of infancy.

Surgical intervention for congenital hyperinsulinism with an unclear focal lesion in the pancreatic head sometimes require the resection of most of the pancreas head and pancreaticojejunotomy. This report presents the case of a patient that underwent pancreatic head resection preserving the main pancreatic duct to avoid pancreaticojejunostomy.

Specific conformation and Ca(2+)-binding mode of yeast calmodulin: insight into evolutionary development.

The vertebrate calmodulin is configured with two structurally independent globular lobes in N- and C-terminus, and a flexible central linker. Distinctly, two lobes of calmodulin from Saccharomyces cerevisiae (yCaM) interact and influence the Ca(2+)-binding profile of each other. We explored this further using the mutant proteins with eliminated Ca(2+)-binding ability in one of the lobes and found that the Ca(2+)-bound N-lobe associates with the Ca(2+)-free C-lobe to gain the Ca(2+) affinity of a wild-type level.

Ran and calcineurin can participate collaboratively in the regulation of spermatogenesis in scallop.

Calcineurin is a calcium/calmodulin-dependent protein phosphatase that plays important roles in the transduction of calcium signals in a variety of tissues. In addition, calcineurin has been implicated in the process of spermatogenesis. A novel calcineurin-binding protein, CaNBP75, has been identified in scallop testis.

Partial internal biliary diversion for patients with progressive familial intrahepatic cholestasis type 1.

We herein report a case of progressive familial intrahepatic cholestasis with partial internal biliary diversion (PIBD). Although by using PIBD an external stoma can be avoided, exposure of the ileocecal junction to bile reflux as well as the effects of the direct bile flow on the colonic mucosa require further investigation.

Kawasaki disease-associated MERS: pathological insights from SPECT findings.

We report for the first time the single photon emission computed tomography (SPECT) findings of a patient with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) associated with Kawasaki disease, which showed hypoperfusion of the bilateral cingulate gyri, thalamus, basal ganglia, brainstem, and cortex of the frontal lobes. These findings indicate that the pathogenesis of MERS is based on cerebral hypoperfusion due to vasculitis or cerebrovascular dehydration.

Roles of the C-terminal residues of calmodulin in structure and function.

Electrospray ionization mass spectrometry (ESI-MS), circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy, flow dialysis, and bioactivity measurements were employed to investigate the roles of the C-terminal residues of calmodulin (CaM). In the present study, we prepared a series of truncated mutants of chicken CaM that lack four (CCMΔ4) to eight (CCMΔ8) residues at the C-terminal end. It was found that CCMΔ4, lacking the last four residues (M145 to K148), binds four Ca ions.

Conformation of the calmodulin-binding domain of metabotropic glutamate receptor subtype 7 and its interaction with calmodulin.

Calmodulin (CaM), a Ca(2+)-binding protein, is a well-known regulator of various cellular functions. One of the targets of CaM is metabotropic glutamate receptor 7 (mGluR7), which serves as a low-pass filter for glutamate in the pre-synaptic terminal to regulate neurotransmission. Surface plasmon resonance (SPR), circular dichroism (CD) spectroscopy and nuclear magnetic spectroscopy (NMR) were performed to study the structure of the peptides corresponding to the CaM-binding domain of mGluR7 and their interaction with CaM.

Fortilin binds Ca2+ and blocks Ca2+-dependent apoptosis in vivo.

Fortilin, a 172-amino-acid polypeptide present both in the cytosol and nucleus, possesses potent anti-apoptotic activity. Although fortilin is known to bind Ca2+, the biochemistry and biological significance of such an interaction remains unknown. In the present study we report that fortilin must bind Ca2+ in order to protect cells against Ca2+-dependent apoptosis.

Spine and rib abnormalities and stature in spondylocostal dysostosis.

Study Design: A retrospective study of radiographic and clinical findings of spondylocostal dysostosis.

Objective: To determine the features of spondylocostal dysostosis diagnosed using consistent diagnostic criteria.

Summary Of Background Data: To our knowledge, no clear definition of spondylocostal dysostosis exists, and little information is available regarding its clinical or radiographic features.

Al(3+) interaction sites of calmodulin and the Al(3+) effect on target binding of calmodulin.

The interaction between calmodulin (CaM) and Al(3+) was studied by spectroscopic methods. Heteronuclear two-dimensional NMR data indicated that peaks related to the both lobes and middle of the central helix of CaM are largely affected by Al(3+). But chemical shift perturbation suggested that overall conformation of Ca(2+)-loaded CaM is not changed by Al(3+) binding.

Identification and characterization of a novel calcineurin-binding protein in scallop testis.

Calcineurin has been inferred to function in meiosis and spermiogenesis in testis. Here, we identified a calcineurin-binding protein in scallop testis by Far-Western blot analysis using purified calcineurin as a probe. The molecular mass of the binding protein estimated on the blot was 75 kDa.

Genomic structure of the sponge, Halichondria okadai calcyphosine gene.

Calcyphosine is an EF-hand Ca(2+)-binding protein, which was first isolated from the canine thyroid. It is phosphorylated in a cyclic AMP (cAMP)-dependent manner; then it is thought to be implicated in the cross-signaling between the cAMP and calcium-phosphatidylinositol cascades. Here, we isolated the DNA complementary to RNA (cDNA) of an EF-hand Ca(2+)-binding protein from the sponge, Halichondria okadai and determined its genomic structure.

Favorable outcome in a case of perinatal enterovirus 71 infection.

A 5-day-old newborn baby presented with skin eruption, oral vesicles, and fever. His mother developed skin eruption at the same time, and his four-year-old sister was diagnosed with hand-foot-mouth disease 1 week before his delivery. Enterovirus 71 was isolated from cerebrospinal fluid that showed mild pleocytosis.