Exome sequencing in developmental eye disease leads to identification of causal variants in GJA8, CRYGC,PAX6 and CYP1B1

Developmental eye diseases, including cataract/microcornea, Peters anomaly and coloboma/microphthalmia/anophthalmia, are caused by mutations encoding many different signalling and structural proteins in the developing eye. All modes of Mendelian inheritance occur and many are sporadic cases, so provision of accurate recurrence risk information for families and affected individuals is highly challenging. Extreme genetic heterogeneity renders testing for all known disease genes clinically unavailable with traditional methods. We used whole-exome sequencing in 11 unrelated developmental eye disease patients, as it provides a strategy for assessment of multiple disease genes simultaneously. We identified five causative variants in four patients in four different disease genes, GJA8, CRYGC, PAX6 and CYP1B1. This detection rate (36%) is high for a group of patients where clinical testing is frequently not undertaken due to lack of availability and cost. The results affected clinical management in all cases. These variants were detected in the cataract/microcornea and Peters anomaly patients. In two patients with coloboma/microphthalmia, variants in ABCB6 and GDF3 were identified with incomplete penetrance, highlighting the complex inheritance pattern associated with this phenotype. In the coloboma/microphthalmia patients, four other variants were identified in CYP1B1, and CYP1B1 emerged as a candidate gene to be considered as a modifier in coloboma/microphthalmia.     

Detection of Clostridium difficile toxin: comparison of enzyme immunoassay results with results obtained by cytotoxicity assay

Several kinds of laboratory techniques are available to detect Clostridium difficile toxin in fecal samples. Because questions have been raised about the reliability of immunoassays compared to the accepted standard, cytotoxicity assay, we studied three enzyme immunoassays (EIAs) and one rapid EIA, which demonstrated relatively good sensitivities and specificities compared to cytotoxicity assay.     

Ductal paucity and Warkany syndrome in a patient with congenital extrahepatic portocaval shunt

An eleven-year-old clinically dysmorphic and devel-opmentally retarded male child presenting with com-plaints of 5 episodes of recurrent cholestatic jaundice since 3 years of age was evaluated. Imaging revealed features consistent with congenital extrahepatic porto-caval shunt(Abernethy type 1b), multiple regenerative liver nodules and intrahepatic biliary radical dilatation. The presence of ductal paucity and trisomy 8 were con-firmed on liver biopsy and karyotyping. The explanation for unusual and previously unreported features in the present case has been proposed.     

Ipsilateral keratoconus associated with long-standing primary hydatid cyst of the orbit

Hydatid cyst is a cyclozoonotic infection of the larvae form of a platyhelminthes Echinococcus granulosus. The majority of hydatid cysts appear in the liver (65%) and lungs (25%). Kidneys and brain are other less common sites for this disease. Only 1% to 2% cases are seen in the maxillofacial region. These commonly appear as cystic lesions located in the mandible, maxillary sinus, orbit, infratemporal fossa, pterygopalatine fossa, parapharyngeal space, tongue, and parotid and submandibular salivary gland. Hydatid cysts of the orbit are rare and account for 1% of all hydatid cysts. The article presents hydatid cyst of the orbit in a 10-year-old child. Clinical features, investigations, surgical approaches, and adjuvant medical management have been emphasized. We believe that the lateral orbital route allows excellent exposure and safe removal of an intraorbital hydatid cyst located posteriorly, superiorly, and laterally without damaging the surrounding important orbital structures. Upper blepharoplasty incision results in good cosmetic outcome.     

Genetic heterogeneity in northeastern India: Reflection of Tribe–Caste continuum in the genetic structure

We critically examined the gene frequency data for 11 genetic markers commonly available in the literature for 22 populations of northeastern India in the light of their geographic, linguistic, and ethnic affiliations. The markers investigated were three blood groups (A₁A₂BO, MNS, and Rh), four serum proteins (KM, Gc, Hp, and Tf), and four enzyme systems (AP, AK, EsD, and Hb). The neighbor‐joining tree and multidimensional scaling of the distance matrix suggest relatively high genetic differentiation among the Mongoloid groups, with probably diverse origins when compared to the Caucasoid Indo‐European populations, which had probably come from relatively more homogeneous backgrounds. Broadly speaking, the pattern of population affinities conforms to the ethno‐historic, linguistic, and geographic backgrounds. An interesting and important feature that emerges from this analysis is the reflection of the effect of the sociological process of a Tribe–Caste continuum on genetic structure. While on one end we have the cluster of Caucasoid caste populations, the other end consists of Mongoloid tribal groups. In between are the populations which were originally tribes but now have become semi‐Hinduized caste groups, viz., Rajbanshi, Chutiya, and Ahom. These groups have currently assumed caste status and speak Indo‐European languages. Therefore, one may infer that what appears to be a purely sociological phenomenon of a Tribe–Caste continuum may well reflect in their genetic structure. Am. J. Hum. Biol. 16:334–345, 2004. © 2004 Wiley‐Liss, Inc.     

Arginine extravasation leading to skin necrosis

Arginine hydrochloride is used in the evaluation of short stature and in the management of urea cycle disorders. In recent times, it has been used in the treatment of stroke-like episodes of MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes). We want to highlight the need for good intravenous access and monitoring the drip site to prevent extravasation injuries that can be caused by arginine, which is a hyperosmolar solution.     

Defining the learning curve in robot-assisted thoracoscopic lobectomy

Background

Robot-assisted thoracoscopic lobectomy has been shown to be a safe approach to pulmonary lobectomy. This study sought to define, mathematically, the learning curve for RATS lobectomy.