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Although rare, 3p microdeletion cases have been well described in the clinical literature. The clinical phenotype includes; intellectual disability (ID), growth retardation, facial dysmorphism, and cardiac malformations. Advances in chromosome microarray (CMA) testing narrowed the 3p25 critical region to a 124 kb region, and recent Whole Exome Sequencing (WES) studies have suggested that the SETD5 gene contributes significantly to the 3p25 phenotype. Loss-of-Function (LoF) variants in SETD5 are now considered a likely cause of ID. We report here a patient with a frameshift LoF variant in exon 12 of SETD5. This patient has features overlapping with other patients described with LoF SETD5 variants to include; similar facial morphology, feeding difficulties, ID, behavioral abnormalities and leg length discrepancy. In addition, he presents with an aberrant blind ending bronchus. This report adds to publications describing intragenic mutations in SETD5 and supports the assertion that de novo LoF mutations in SETD5 present with an overlapping but distinct phenotype in comparison with 3p25 microdeletion syndromes.

Background\ud \ud Osteogenesis imperfecta (OI), the commonest inherited bone fragility disorder, affects 1 in 15,000 live births resulting in frequent fractures and reduced mobility, with significant impact on quality of life. Early diagnosis is important, as therapeutic advances can lead to improved clinical outcome and patient benefit.\ud \ud Report\ud \ud Whole exome sequencing in patients with OI identified, in two patients with a multi-system phenotype, compound heterozygous variants in NBAS (neuroblastoma amplified sequence). Patient 1: NBAS c.5741G > A p.(Arg1914His); c.3010C > T p.(Arg1004*) in a 10-year old boy with significant short stature, bone fragility requiring treatment with bisphosphonates, developmental delay and immunodeficiency. Patient 2: NBAS c.5741G > A p.(Arg1914His); c.2032C > T p.(Gln678*) in a 5-year old boy with similar presenting features, bone fragility, mild developmental delay, abnormal liver function tests and immunodeficiency.\ud \ud Discussion\ud \ud Homozygous missense NBAS variants cause SOPH syndrome (short stature; optic atrophy; Pelger-Huet anomaly), the same missense variant was found in our patients on one allele and a nonsense variant in the other allele. Recent literature suggests a multi-system phenotype. In this study, patient fibroblasts have shown reduced collagen expression, compared to control cells and RNAseq studies, in bone cells show that NBAS is expressed in osteoblasts and osteocytes of rodents and primates. These findings provide proof-of-concept that NBAS mutations have mechanistic effects in bone, and that NBAS variants are a novel cause of bone fragility, which is distinguishable from ‘Classical’ OI.\ud \ud Conclusions\ud \ud Here we report on variants in NBAS, as a cause of bone fragility in humans, and expand the phenotypic spectrum associated with NBAS. We explore the mechanism underlying NBAS and the striking skeletal phenotype in our patients.

Background In 1993, Chitayat et al. , reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise. Objective(s) To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism. Methods Through ongoing collaboration, we had collected patients with strikingly-similar phenotype. Trio-based exome sequencing was first performed in Patient 2 through Deciphering Developmental Disorders study. Proband-only exome sequencing had previously been independently performed in Patient 4. Following identification of a candidate gene variant in Patient 2, the same variant was subsequently confirmed from exome data in Patient 4. Sanger sequencing was used to validate this variant in Patients 1, 3; confirm paternal inheritance in Patient 5. Results A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in ERF was identified in five affected individuals: de novo (patient 1, 2 and 3) and inherited from an affected father (patient 4 and 5). p.Tyr89Cys is an aromatic polar neutral to polar neutral amino acid substitution, at a highly conserved position and lies within the functionally important ETS-domain of the protein. The recurrent ERF c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome. Discussion ERF variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis. Conclusions We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in ERF .

Prompt and accurate diagnosis of skeletal dysplasias can play a crucial role in ensuring appropriate counseling and management (both antenatal and postnatal). When a skeletal dysplasia is detected during the antenatal period, especially early in the pregnancy, it can be associated with a poor prognosis. It is important to make a diagnosis in antenatal presentation of skeletal dysplasias to inform diagnosis, predict prognosis, provide accurate recurrence risks, and options for prenatal genetic testing in future pregnancies. Prenatal ultrasound scanning is a useful tool to detect several skeletal dysplasias and sonographic measurements serve as reliable indicators of lethality. The lethality depends on various factors including gestational age at which features are identified, size of the chest and progression of malformations. Although, it is important to type the skeletal presentation as accurately as possible, this is not always possible in an antenatal presentation and it is important to acknowledge this uncertainty. In the case of a live birth, it is always important to reassess the infant. Osteogenesis imperfecta (OI) is a heterogeneous group of disorders characterized by fragile bones. Here, we report an infant with severe OI born following a twin pregnancy in whom the bone disease is caused by a heterozygous pathogenic mutation, c.4160C >T, p.(Ala1387Val) located in the C-propeptide region of COL1A1. An assumption of lethality antenatally complicated his management in early life. We discuss this patient with particular emphasis on the neonatal presentation of a severe skeletal dysplasia and the lessons that may be learned in such situations. © 2016 Wiley Periodicals, Inc.

Neonatal diabetes and hypothyroidism (NDH) syndrome was first described in 2003 in a consanguineous Saudi Arabian family where two out of four siblings were reported to have presented with proportionate IUGR, neonatal non-autoimmune diabetes mellitus, severe congenital hypothyroidism, cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by enlarged kidneys and multiple small cysts with deficient cortico-medullary junction differentiation and normal kidney function. There was minor facial dysmorphism (depressed nasal bridge, large anterior fontanelle, long philtrum) reported but no facial photographs were published. Mutations in the transcription factor GLI-similar 3 (GLIS3) gene in the original family and two other families were subsequently reported in 2006. All affected individuals had neonatal diabetes, congenital hypothyroidism but glaucoma and liver and kidney involvement were less consistent features. Detailed descriptions of the facial dysmorphism have not been reported previously. In this report, we describe the common facial dysmorphism consisting of bilateral low-set ears, depressed nasal bridge with overhanging columella, elongated, upslanted palpebral fissures, persistent long philtrum with a thin vermilion border of the upper lip in a cohort of seven patients with GLIS3 mutations and report the emergence of a distinct, probably recognizable facial gestalt in this group which evolves with age. © 2016 Wiley Periodicals, Inc.

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. It exhibits a broad spectrum of clinical severity, ranging from multiple fractures in utero and perinatal death, to normal adult stature and low fracture incidence. Extra-skeletal features of OI include blue sclera, hearing loss, skin hyperlaxity, joint hyperextensibility, and dentinogenesis imperfecta. The proα1(I) and proα2(I) chains of collagen 1 are encoded by the COL1A1 and COL1A2 genes, respectively; quantitative or qualitative defects in type I collagen synthesis usually manifest as types of OI or some sub-types of EDS. The majority of patients (about 90%) with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2 genes, which shows an autosomal dominant pattern of inheritance. Six other genes, CRTAP, LEPRE1, FKBP10, PP1B, SP7/Osterix (OSX), and SERPINH1, are associated with autosomal recessive forms of OI. However, other, rare phenotypes have also been described. There are many differential diagnoses of the short, syndromic child, including chromosomal, single gene, and multifactorial causes. However, one condition of particular relevance in the context of this report is the Russell-Silver syndrome (RSS). As originally described, the RSS is a very specific condition. However, it has subsequently become an umbrella term for a heterogeneous group of conditions presenting with short stature and triangular shape to the face. A significant proportion of these are now believed to be due to imprinting defects at 11p15. However, the cause in many cases remains unknown. We describe two cases with a phenotypic overlap between OI and RSS who both have COL1A1 mutations. Thus, a type 1 collagenopathy should be considered in the differential diagnosis of syndromic short stature.

IMAGe syndrome is a rare condition, first reported by Vilain et al., in 1999, characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and commenced on steroid replacement therapy. Other reported features in this condition include, hypercalciuria and/or hypercalcemia, craniosynostosis, cleft palate, and scoliosis. We report on a 7-year-old boy with IMAGe syndrome, who in addition to the features in the acronym also has bilateral sensorineural hearing loss which has not been reported in previously published cases of IMAGe syndrome. We discuss the clinical presentation in our patient and review the literature in this rare multisystem disorder.

Epidermolytic hyperkeratosis (EHK; OMIM 113800), or epidermolytic ichthyosis (EI), is a rare autosomal dominant skin disorder characterized by erythroderma and blistering at birth, which is replaced by progressive hyperkeratosis. In most cases, EHK/EI is due to dominant mutations in the genes encoding keratin 1 or keratin 10. A recessive form of EHK/EI has been described caused by truncating mutations in the KRT10 gene. Here, we report two male siblings with EHK/EI in whom we have identified a novel homozygous mutation, KRT10 c.1A>T. We discuss the importance of establishing the mode of inheritance in EHK. We also discuss the varying presentation of a ‘collodion baby’, and the differential diagnosis to consider. The histopathological and ultrastructural changes in both forms of EHK/EI have subtle differences that are detailed, and the importance of identifying these key features to target molecular analysis is further explained. These cases highlight the value of a dedicated skin genetics clinic with high...

The toxicity of fenvalerate to the prawn Penaeus monodon was evaluated using biomarkers of stress. In a preliminary bioassay test, P. monodon was exposed to a series of fenvalerate concentrations, which showed 4, 6.5 and 8.5 μg L −1 to be sublethal, median lethal and lethal, respectively. Sublethal effect of fenvalerate was further evaluated in hepatopancreas, muscle and gills of prawns with reference to oxidative stress biomarkers. Significant induction of lipid peroxidation and glutathione- S -transferase activity was found in hepatopancreas, muscle and gills of prawns exposed to fenvalerate when compared to control ( P P P

Interaction of potash and decis in the ecophysiology of a freshwater fish, Oreochromis mossambicus , was studied. It was found that 300, 550 and 700 mg L −1 of potash were sublethal (LC 0 ), median lethal (LC 50 ), and toxic (LC 100 ) to O. mossambicus for 96 h exposure, respectively. For decis, 96 h LC 100, LC 50 , and LC 0 was 0.4, 0.25, and 0.1 mg L −1 , respectively. Sublethal concentrations of potash and decis were exposed to fishes individually and in combination for 28 days. The results revealed that the combined effect of these chemicals was more highly toxic to food intake, growth, and conversion efficiencies than the individual chemicals. The marker enzymes (acid phosphatase, alkaline phosphatase, aspartate transaminase, alanine transaminase) were also analyzed in blood, liver and muscle. The enzyme activities were decreased in liver and muscle. On the other hand, serum exhibited increased activities of marker enzymes. The results were tested statistically and interpreted accordingly.

Duplications of 18p have been reported in the literature associated with a range of different abnormalities and also in patients with normal phenotypes. The majority of these reports are based solely on G-banded cytogenetic evaluation. The use of arrayCGH characterization has improved the ability to define regions of imbalance and is helping to identify potential underlying triplosufficiency of any duplicated genes. We report on a family where the father and his two daughters all have a duplication 18p11.32-p11.31 characterized by microarray. They present with variable levels of intellectual disability/developmental delay and behavioural difficulties without any physical anomalies. This family contributes toward the growing knowledge of pure duplications of 18p and provides information on interpretation of novel array findings in the context of family history. It also reiterates the importance of elucidating a detailed learning and developmental phenotype and family pedigree in aiding interpretation of genetic testing results.

Sublethal effect of monocrotophos (pesticide) and ammonium chloride (fertilizer) was studied in the freshwater fish Oreochromis mossambicus, with reference to carbohydrate metabolism for a period of 96 h. The glycogen content was analysed in liver and muscle, while the lactate and pyruvate were assessed in blood along with liver and muscle. The results revealed that the glycogen content was found to be decreasing. In contrast increase in the tissues lactate and pyruvate level was found in the fishes exposed to pesticide and fertilizer individually and in combinations. The combined effects of these chemicals were more toxic to carbohydrate metabolism than the effect produced by the individual chemicals. The results were tested to search for statistical significance. The calculated lactate and pyruvate ratio (L/P) indicated that the fishes were under chemical stress.

To document the impact of naphthalene, a comparative toxicological research was performed in the estuarine crab Scylla tranquebarica habitant of Ennore creek (polluted site) and Kovalam creek (pristine site) for a period of 6 months. The biochemical constituents, such as protein, carbohydrate, lipid and enzyme activities like acid and alkaline phosphatase, aspartate and alanine transaminase were analysed in hepatopancreas, heamolymph and ovary of the female crabs collected from the two creeks. The results revealed that there was a significant measurable difference in these parameters in the tissues of crabs sampled from the polyaromatic hydrocarbon (PAH) polluted site (Ennore creek) when compared with the reference site (Kovalam creek). In addition naphthalene was detected in gill, hepatopancrease, heamolymph and ovary of the crabs sampled from the polluted creek. The results indicate that the indicators selected for toxic impact in S. tranquebarica may be related to the uptake of naphthalene in the tissues examined and support the feasibility of employing these types of analyses as biochemical biomarkers for PAH contaminant-exposed organisms.

The sublethal effects of naphthalene on protein, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), carbohydrates, lipids, and certain marker enzymes such as phosphatases, transaminases, and lactate dehydrogenase were studied in hepatopancreas, hemolymph, and ovary in the edible crab Scylla serrata. The results revealed that there was overall decrease in total protein, total DNA, total RNA, free sugar, glycogen, protein-bound sugars, neutral lipid, glycolipid, and phospholipid in the test samples compared to control. Similarly all the marker enzymes (acid phosphatase, alkaline phosphatase, aspartate transaminase, alanine transaminase, and lactate dehydrogenase) were decreased in hepatopancreas and ovary. On the other hand, in hemolymph, the activities of marker enzymes were increased. The results were tested statistically and interpreted accordingly.

The effects of urea on survival, food utilization and oxygen consumption of the fresh water fish Oreochromis mossambicus were studied. The percentage survival of O. mossambicus when exposed to different concentrations of urea at 24, 48, 72 and 96 h exposures was noted and it was found that 22,000 and 38,000 mg L −1 urea concentration were sublethal and lethal, respectively. The median lethal concentration, which killed 50% of the fishes during 96 h exposure, was 28,000 mg L −1 . Rearing the fish in increasing sublethal concentrations of urea, it was found that the feeding rate decreased from 34.341 ± 7.067 mg g live fish −1 d −1 (control) to 13.921 ± 2.315 mg g live fish −1 d −1 at the highest concentration of urea (22,000 mg L −1 ). Growth rate was drastically reduced. The consumption of oxygen in O. mossambicus diminished from 0.962 ± 0.208 to 0.645 ± 0.118 mg g live fish −1 h −1 when reared in the highest sublethal concentration of urea.

Conductometry, circular dichroism and fluorescence spectroscopy are thetechniques employed to investigate the effect of added calcium ions and other monovalent and divalent metal ions on aqueous solutions of nonionic peptide aggregates, Boc-Leu-Asn-OEt (1). It is observed that among all the metal ions studied, Ca2+ ions facilitate the aggregation of the peptide. The interior dielectric constant of the micelles (e) was found to depend upon the proportion of Ca2+ complexed peptide with the peptide monomers in the micelles. When Ca2+ ion becomes 1/4th of the peptide concentration, there is a structural transition leading to drastic change in the interior of the micro dielectric constant (em).

We report a fetus with mosaic trisomy 11 who also had bilateral renal agenesis. We describe the post-mortem examination findings in the fetus and cytogenetic analysis. There are no earlier reports of full trisomy 11, presumably because it is lethal and results in early spontaneous miscarriages. There is only one report published earlier in a fetus with mosaic trisomy 11. There have been a few case reports of trisomy 11 identified in pre-natal samples, where it was associated with normal outcome. Bilateral renal agenesis has not been reported earlier in association with mosaic nor non-mosaic trisomy 11. We describe this rare cytogenetic finding in a fetus with bilateral renal agenesis. We also discuss the issues around genetic counselling when this is encountered in clinical practice.

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity for fractures. It is a variable condition with a range of clinical severities. The histological and ultrastructural findings in the skin of patients with OI have not been described in detail in the previously published literature. Although protein analysis of cultured fibroblasts has historically been used in the diagnostic work-up of OI patients, other aspects of skin examination are not routinely performed as part of the diagnostic pathway in patients with OI. The aims of this study were to perform histological and ultrastructural examination of skin biopsies in patients with OI. This was to identify common and distinguishing features in the numerous genetically distinct subtypes of OI and compare the findings with those in patients who did not present with fractures, and to enable the use of the results thus obtained to aid in the diagnostic work-up of patients with OI. As part of a larger research study set-up to identify clinical features and natural history in patients with atypical features of OI, skin biopsy and examination (histology and electron microscopy) were undertaken. Genetic analysis and ancillary investigations were also performed to identify similarities within this group and to differentiate this group from the 'normal' population. At the end of this study, we were able to demonstrate that the histological and electron microscopic findings on a skin biopsy may be an indicator of the likelihood of identifying a pathogenic mutation in type 1 collagen genes. This is because patients with specific findings on examination, such as elastic fibre area fraction (on histological analysis), collagen fibril diameter variability, deviation from the expected mean and collagen flowers (on electron microscopy), are more likely to be positive on genetic analyses. This has, in turn, provided more insight into the pathways to direct gene testing and has reinforced the need for accurate phenotyping before undertaking further genetic investigations. The morphometric assessment of elastic fibre area fraction and ultrastructural findings from this study have provided us with a better understanding of OI and insights into the possible mechanism of these changes in the skin. Correlation of skin findings with the clinical phenotype as well as genetic testing has enabled understanding of the molecular pathogenesis and translation of changes at the genomic level to clinical phenotype.

Zimmerman–Laband syndrome is a rare genetic disorder characterized by gingival fibromatosis, dysplastic or absent nails, hypoplasia of the distal phalanges, scoliosis, hepatosplenomegaly, hirsutism and abnormalities of the cartilage of nose and/or ears. We would like to give an update on the progres

The effects of naphthalene on glycogen, lipid, phosphatases and esterase have been studied in the muscle and ovary of Intermoult marine female crab, Scylla serrata. Rearing the crab in increasing sublethal concentrations of naphthalene for 96 hr (i.e. 0.005, 0.010, 0.015 and 0.020 mg L-1). The results show an overall decrease in the glycogen, lipid, alkaline phosphatase and esterase in muscle and ovary. On the other hand, acid phosphatase activity in the muscle and ovary has increased.

The effects of ammonium chloride on survival and feeding energetics of the freshwater fish Oreochromis mossambicus were studied. At a concentration of 600 mg L-1 ammonium chloride, 100% mortality was observed within 24 h; no mortality occurred at 400 mg L-1 within 96 h; Concentration of 450 mg L-1 ammonium chloride was found as median lethal concentration at 96 h exposure. Rearing the fish in increasing sublethal concentrations of ammonium chloride, it was found that the feeding rate decreased from 20.309 ± 0.506 mg g live fish-1 day-1 (mg g-1 d-1 (control) to 11.594 ± 0.479 mg g-1 d-1 at the highest sublethal concentration (100 mg L-1. Growth rate was drastically reduced.

Somatic mutations in the phosphatidylinositol/AKT/mTOR pathway cause segmental overgrowth disorders. Diagnostic descriptors associated with PIK3CA mutations include fibroadipose overgrowth (FAO), Hemihyperplasia multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal (CLOVES) syndrome, macrodactyly, and the megalencephaly syndrome, Megalencephaly-Capillary malformation (MCAP) syndrome. We set out to refine the understanding of the clinical spectrum and natural history of these phenotypes, and now describe 35 patients with segmental overgrowth and somatic PIK3CA mutations. The phenotypic data show that these previously described disease entities have considerable overlap, and represent a spectrum. While this spectrum overlaps with Proteus syndrome (sporadic, mosaic, and progressive) it can be distinguished by the absence of cerebriform connective tissue nevi and a distinct natural history. Vascular malformations were found in 15/35 (43%) and epidermal nevi in 4/35 (11%) patients, lower than in Proteus syndrome. Unlike Proteus syndrome, 31/35 (89%) patients with PIK3CA mutations had congenital overgrowth, and in 35/35 patients this was asymmetric and disproportionate. Overgrowth was mild with little postnatal progression in most, while in others it was severe and progressive requiring multiple surgeries. Novel findings include: adipose dysregulation present in all patients, unilateral overgrowth that is predominantly left-sided, overgrowth that affects the lower extremities more than the upper extremities and progresses in a distal to proximal pattern, and in the most severely affected patients is associated with marked paucity of adipose tissue in unaffected areas. While the current data are consistent with some genotype–phenotype correlation, this cannot yet be confirmed. © The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.

We describe two unrelated patients with molecularly confirmed Sotos syndrome with multiple subpleural blebs and pneumothorax. We propose this as a new association. Patient 1 is a 3-year-old boy with a 1.9Mb interstitial deletion of the long arm of chromosome 5, with breakpoints at q35.2 and q35.3, encompassing NSD1 and Patient 2 is a 9-year-old girl with a de novo truncating mutation within NSD1. Both patients presented with sudden onset dyspnea due to a unilateral pneumothorax: Patient 1 at the age of 18 months and Patient 2 at 9 years. In both, the pneumothorax recurred following removal of the chest drain and, on further investigations, multiple subpleural blebs were identified necessitating a pleurodesis and tissue resection. This is the first report of multiple subpleural blebs leading to pneumothorax in association with Sotos syndrome. Given the similar and unusual presentation in the two affected patients, we suggest that this may be a real association, albeit a rare one. While screening would not be advocated for such a rare association, we recommend that clinicians consider pneumothorax in patients with Sotos syndrome and sudden onset of dyspnea and are aware that it may be refractory to first line treatment. (c) 2014 Wiley Periodicals, Inc.

We report two families with a variable presentation in association with a KRIT1 mutation. The index patient in Family 1 was a 9-year old girl who presented with left hemi-dystonia and a cerebral cavernous malformation was identified in the right lentiform nucleus. The maternal grandmother presented with a spinal cavernoma, which was operated at 35-years of age. The mother presented with intractable temporal lobe epilepsy in childhood and underwent temporal lobe resection at 27-years of age. The second family has also presented variably with the youngest member of this family presenting with generalised tonic-clonic seizures at 18-months of age. We report both these families with variable presentation of an autosomal dominant condition and describe the phenotypic presentation in both these families in further detail and review the published literature on this condition.

International audience; Recurrent deletions of 2q32q33 have recently been reported as a new microdeletion syndrome, clinical features of which include significant learning difficulties, growth retardation, dysmorphic features, thin and sparse hair, feeding difficulties and cleft or high palate. Haploinsufficiency of one gene within the deleted region, SATB2, has been suggested to be responsible for most of the features of the syndrome. We describe seven previously-unreported patients with deletions at 2q33.1, all partially overlapping the previously-described critical region for the 2q33.1 microdeletion syndrome. The deletions ranged in size from 35 kb to 10.4 Mb, with the smallest deletion entirely within the SATB2 gene. Patients demonstrated significant developmental delay and challenging behaviour, a particular behavioural phenotype that seems to be emerging with more reported patients with this condition. One patient in our cohort has a deletion entirely within SATB2 and has a cleft palate, whereas several patients with larger deletions have a high-arched palate. In addition, one other patient has significant orthopaedic problems with ligamentous laxity. Interestingly, this patient has a deletion that lies just distal to SATB2. The orthopaedic problems have not been reported previously and are possibly an additional feature of this syndrome. Overall, our report provides further evidence that the SATB2 gene is the critical gene in this microdeletion syndrome. In addition, because the individuals in our study range in age from 3 to 19 years, these patients will help define the natural progression of the phenotype in patients with this microdeletion.

Chromosome 16p13.11 has recently been reported as a region of recurrent microdeletion/duplication, which may contribute to a specific clinical phenotype of epilepsy, significant learning difficulties and distinct facial dysmorphism. The 16p13.11 microdeletion syndrome is associated with schizophrenia, developmental delay and idiopathic generalised epilepsy. Haploinsufficiency of genes in 16p13.11 has been suggested as contributing to the pathogenicity of this microdeletion syndrome. We report a three-year-old boy with the 16p13.11 microdeletion syndrome, identified on array CGH, and describe his clinical phenotype, thereby adding to the existing literature on this newly-described microdeletion syndrome. We discuss the function and potential relevance of the genes in this region with regards to the features described in this condition.

Congenital pancreatic hypoplasia is a rare cause of neonatal diabetes. We report on a series of three patients with pancreatic agenesis and congenital heart defects. All had abdominal scan evidence of pancreatic agenesis. In addition, Patient 1 had a ventricular septal defect, patent ductus arteriosus and pulmonary artery stenosis; Patient 2 had a truncus arteriosus and Patient 3 had tetralogy of Fallot. Two of the three patients have developmental delay. All three patients were isolated cases within the family. Investigations included sequencing of GCK, ABCC8, IPF1, NEUROD1, PTF1A, HNF1B, INS, ISL1, NGN3, HHEX, G6PC2, TCF7L2, SOX4, FOXP3 (Patients 1 and 2), GATA4 and KCNJ11 genes (all three patients), but no mutations were found. Genetic investigation to exclude paternal UPD 6, methylation aberrations and duplications of 6q24 was also negative in all three. 22q11 deletion was excluded in all three patients. Array CGH in Patient (1) showed a approximately 250 kb, paternally inherited duplication of chromosome 12q [arr cgh 12q24.33 (B35:CHR12:131808577-132057649++) pat], not found in the other two patients. Permanent neonatal diabetes mellitus due to pancreatic hypoplasia with congenital heart defects has been reported before and may represent a distinct condition. We discuss this rare association and review previously reported literature.

We report on siblings with probable Adams-Oliver syndrome. The older brother had symmetric intra-uterine growth retardation, plagiocephaly, a cardiac defect and periventricular calcification. The younger sister was born with abdominal and scalp skin defects and small fingers and toes. Prenatal cranial imaging in the younger sibling suggested possible bilateral closed lip schizencephaly and neuronal migrational defect. These siblings are thought to have Adams-Oliver syndrome with the older sibling's features at the milder end of the spectrum while the younger sibling is more severely affected. Several case reports have been published discussing the clinical variability and the possibility of autosomal recessive inheritance. Recently reports suggest an increased frequency of seizures and central nervous system involvement in autosomal recessive Adams-Oliver syndrome. We report affected siblings born to healthy non-consanguineous parents and review previously published similar sibships and case reports in relation to the clinical features.

Reactive oxygen species (ROS) directly or indirectly involves in multistage process of carcinogenesis. Antioxidant activity of methanolic extract of Operculina turpethum stems (MEOT) on 7,12 dimethylbenz(a)anthracene (DMBA) induced breast cancer was investigated in female Sprague-Dawley rats. Changes in the levels of lipid peroxidation and antioxidants system was evaluated in addition to tumour development. Twenty four female rats were divided into four groups: control, DMBA, DMBA+MEOT and MEOT. In the DMBA group, rats were intragastrically administered with 20 mg of DMBA using corn oil as vehicle. Animals of DMBA+MEOT group received a single dose of 20 mg of DMBA dissolved in corn oil intragastrically followed by O. turpethum extract (100 mg/kg body weight), while MEOT group received O. turpethum extract (100 mg/kg body weight) intragastrically daily for a period of 45 days. After the experimental period of 45 days, oxidative stress parameters were assessed in serum, liver and breast of both control and experimental groups. In addition to this, tumour weight of breast was also assessed. A significant increase in lipid peroxidation levels were observed in the tested samples of cancer induced rats while the activities of enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-enzymic antioxidants like glutathione (GSH), ascorbic acid (Vitamin C) and alpha-tocopherol (Vitamin E) were decreased in cancer-bearing animals when compared to control animals. A significant (P0.05) increase in the tumour weight was observed in the breast of DMBA group and the breast tumour weight decreased significantly (P0.05) in the DMBA+MEOT groups. Oral administration of MEOT remarkably reduced the lipid peroxidation activity and increased the antioxidants level in drug treated animals and decreased the tumour weight significantly (P0.05). This result suggests that MEOT shows antioxidant activity and play a protective role against DMBA induced breast cancer.

The Rural road contributes more to our nation development. It contains 59% in the overall country road length. Rural road is the Major factor in the agriculture productivity. Statistic and much study clearly explain Relationship between rural road and agriculture productivity. In India Top five agriculture producing state like Tamil Nadu, Punjab, Himachal Pradesh, Uttra Pradesh and Gujarat has good road density. The road density play importance role in the agriculture productivity. This paper attempts to identify the present condition of rural roads, Farmers need for improve the agriculture productivity, Relationship between road density and agriculture production, compare the road density of Uthiramerur and Madurandagam Taluk with National and State road density. A thorough literature review was done and also expert opinion from developing countries were taken, through which rural road contribute more to agriculture productivity. In number of factors were short-listed to be made part of the survey questionnaire and the survey was conducted with farmers in the village of Uthiramerur and Madurandagam taluk. This study indicated that the present rural road condition not in appreciable position. Government give more attention to agriculture development and Rural road maintenance. The road density found in Uthiramerur and Madurandagam are more than the national and state average road density. The good road density improves the agriculture productivity.

The 30-day sublethal effect of naphthalene on Scylla serrata was studied using hematological parameters, lipid peroxidation, and antioxidant status. The results revealed a decreasing trend in the hemolymph-related parameters of the crabs exposed to naphthalene. There was an increase in lipid peroxidation activity in the gonads of the crabs exposed to naphthalene. On the other hand, the enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and nonenzymatic (vitamin E, vitamin C and glutathione) antioxidants showed decreased activity for the respective gonads. The results were statistically significant in comparison with the control. These parameters are considered the first detectable/quantifiable response to chemical stress and can serve as biomarkers.

The effect of naphthalene on lipid peroxidation and antioxidants status was studied in hepatopancreas, haemolymph and ovary of the Scylla serrata with reference to the active vitellogenic stage. There was an overall increase in lipid peroxidation activity in the tested samples. In contrast, the enzymatic (catalase, glutathione peroxidase, superoxide dismutase) and non-enzymatic antioxidants (vitamins C, E and glutathione) showed decreased activities for hepatopancreas, haemolymph and ovary.

The multiplicity of soluble esterases in Raillietina tetragona, R. echinobothrida and R. cesticillus was studied by use of slab polyacrylamide gel electrophoresis. Five fractions of esterase activity were observed in R. tetragona, seven in R. echinobothrida and three in R. cesticillus. The various fractions of esterase activity of closely related species of Raillietina showed differential behaviour towards various chemicals. Based on the inhibitory effect of inhibitors p-CMB, EDTA, malathion, silver nitrate and eserine sulphate, the various esterases have been classified into arylesterase, carboxylesterase, acetylesterase and cholinesterase.

Soluble esterase isozymes from Raillietina tetragona were separated in polyacrylamide gel electrophoresis, which revealed the presence of at least four fractions, possibly representing different esterases. The differences in the inhibitory effect of various chemicals on these fractions reveal them to be four types of esterases, namely: arylesterase, carboxylesterase, acetylesterase and cholinesterase.

S. mossambicus was exposed to toxic and sublethal concentrations of the fertilizer diammonium phosphate (0.2 to 1.0 g l−1). Mortality, food utilization and growth were studied. At a concentration of 0.6 g l−1 DAP, 100% mortality was observed within 96 h; no mortality occurred at 0.5 g l−1; LC50 was 0.55 g l−1. Rearing the fish in increasing sublethal concentrations of DAP, it was found that the feeding rate decreased from 25.4 mg g−1 fish−1 d−1 (fish reared in DAP-free water) to 10.1 mg g−1 d−1 at the highest sublethal concentration (0.5 g l−1). Growth rate was drastically reduced. At high sublethal concentrations of DAP, the fish lost reserve energy, in addition to the energy obtained from food intake for survival, as a result of increased swimming activity and opercular beats.

Electrophoretic analyses of liver and muscle ofChanna punctatus revealed that they contain atleast six and eight fractions of esterase, respectively. Characterization of esterase was made on the basis of their responses towards certain inhibitors. Liver esterase consists of acetylesterase and carboxyl esterases, whereas the muscle esterase has three types namely acetylesterase, carboxylesterase and cholinesterase. The liver and muscle ofC. Punctatus subjected to maximum sublethal concentration of carbaryl were electrophoretically analysed and it was found that both liver and muscle showed only three fractions of esterase.