Identification of differentially expressed proteins in the aqueous humor of primary congenital glaucoma

Primary Congenital Glaucoma (PCG) is an autosomal recessive disease caused by an abnormal development of the anterior chamber angle. Although, PCG has been linked to several genetic loci, the role that the genes at these loci or their encoded proteins play in the pathophysiology of PCG and development of the anterior chamber is not known. To identify proteins that may be altered in PCG and that may help in understanding the underlying pathophysiology of the disease, we took a global proteomics approach. Tryptic digests of the complex mixtures of proteins in aqueous humor were analyzed using Liquid Chromatography/Mass Spectrometry (LC-MS/MS). Proteins were identified by searching the data against the human subset of the UniProt database. The proteomes of aqueous humor in PCG (n = 7) and patients undergoing cataract surgery as control (n = 4) were compared based on the scan counts of comparable proteins. Using stringent filtering criteria, Apolipoprotein A-IV (APOA-IV), Albumin and Antithrombin 3 (ANT3) were detected at significantly higher levels in PCG AH compared to control, whereas Transthyretin (TTR), Prostaglandin-H2 D-isomerase (PTGDS), Opticin (OPT) and Interphotoreceptor Retinoid Binding Protein (IRBP) were detected at significantly lower levels. Many of these proteins play a role in retinoic acid (RA) binding/transport and have been implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer’s (AD). It is possible that similar to AD, the pathologic changes in PCG during development could be influenced by the availability of RA in the anterior chamber.     

Ocular manifestations in Kabuki syndrome: the first report from Saudi Arabia

Background: Kabuki syndrome (KS) is a multiple congenital anomaly syndrome in which ophthalmological examination for the early detection of ocular abnormalities is desired in order to prevent visual impairment. Case: Retrospective, interventional, case report of a 5-year-old female patient of Arabic origin with features of Kabuki syndrome. Observation: Patient had neurological deficit, psychomotor retardation, a peculiar face, including large prominent cup shaped ears, broad depressed nasal tip, and high arched palate, and malformed teeth. Her ocular features suggestive of Kabuki syndrome included left upper eyelid congenital ptosis, lagophthalmos, arched eyebrows with temporal sparing of hair, long horizontal palpebral fissures, lateral lower eyelid eversion and resultant epiphora. Other abnormalities included medial lower epicanthal folds, abduction deficit bilaterally, large esotropia, significant hyperopia, right corneal opacity, iris and chorioretinal coloboma. Patient required hyperopic correction and ptosis surgery, which improved her visual functioning. Conclusions: We report the first case of a Kabuki syndrome patient from Saudi Arabia and stress on the importance of ophthalmological examination in all patients with KS for the early detection of ocular anomalies in order to prevent visual impairment.     

Comparison of respiratory triggering and gating techniques for the removal of respiratory artifacts in MR imaging

Respiratory movement degrades magnetic resonance (MR) images of the chest and abdomen by increasing noise through the production of "ghost" artifacts and by decreasing edge sharpness in moving structures. Respiratory gating, which limits data acquisition to end-expiration, is successful in restoring edge sharpness and reducing ghosts but increases imaging time two to three times, which limits its use to sequences with short repetition times (TRs). To overcome this limitation, an alternative technique, respiratory triggering, was developed, which triggers the acquisition of an MR section at a fixed point on the respiratory cycle. This technique restores edge sharpness and reduces ghosts, but unlike gating, it can be used to produce an image at any phase of the respiratory cycle. Triggering requires long TRs since the TR is limited to the respiratory period (TP) or one-half of TP, depending on whether the same section is triggered once or twice during a single respiratory cycle. Gating and triggering were evaluated and compared for single-section and multi-section imaging of both volunteers and patients. The authors conclude that when a chest or abdominal survey is required, triggering takes less time than gating if TRs are required that exceed one-fifth of TP.     

Bifid origin of the left vertebral artery

Two patients demonstrating a bifid origin of the left vertebral artery are described. The embryologic origin of this anomaly is reviewed together with diagnostic and therapeutic implications, emphasizing the importance of knowledge and recognition of the anomaly. It is suggested that this anomaly is not as rare as previously thought.     

Subacute and chronic bone infections: diagnosis using In-111, Ga-67 and Tc-99m MDP bone scintigraphy, and radiography

The usefulness of indium-111 white blood cell scintigraphy in the diagnosis of subacute or chronic bone infection was examined in 21 orthopedic patients. In-111 WBC imaging was compared with gallium-67 and technetium-99m methylene diphosphonate skeletal scintigraphy and bone radiography, all studies being performed within 1 week. In-111 WBC scintigraphy showed no definite advantage over Ga-67 scintigraphy in the identification of chronic bone infection. The two tests had the same sensitivity (80%) and similar specificity (In-111 WBC 75%, Ga-67 83%; difference not significant). Bone radiography had a sensitivity of 60% and a specificity of 67%. A negative Tc-99m MDP bone scintigram ruled out infection (sensitivity 100%), but because of low specificity (25%), final evaluation required performance of Ga-67 or In-111 WBC scintigraphy.     

High expression of Lewis<Superscript>y/b</Superscript>antigens is associated with decreased survival in lymph node negative breast carcinomas

Introduction  

There is sufficient evidence that blood group related Lewis antigens are tumour-associated molecules. The Lewis^y and Lewis^b antigens are complex carbohydrates that are over-expressed by breast, lung, colon and ovarian cancers. The SC101 mAb is a unique Lewis^y/b binding antibody that binds to native and extended Lewis^y and Lewis^b haptens, displaying no cross reactivity with H type 1, H type 2, Lewis^x or normal blood group antigens.     

A novel truncating variant in ring finger protein 113A (RNF113A) confirms the association of this gene with X‐linked trichothiodystrophy

We describe an 11‐year old boy with severe global developmental delays, failure to thrive and growth retardation, refractory seizures with recurrent status epilepticus, hypogammaglobulinemia, hypergonadotropic hypogonadism, and duodenal strictures. He had facial and skin findings compatible with trichothiodystrophy, including sparse and brittle hair, thin eyebrows, and dry skin. Exome sequencing showed a hemizygous, truncating variant in RNF113A, c.903_910delGCAGACCA, predicting p.(Gln302fs*12), that was inherited from his mother. Although his clinical features overlap closely with features described in the two previously reported male first cousins with RNF113A loss of function mutations, the duodenal strictures seen in this patient have not been reported. Interestingly, the patient's mother had short stature and 100% skewed X‐inactivation as seen in other obligate female carriers. A second male with developmental delays, microcephaly, seizures, ambiguous genitalia, and facial anomalies that included sparse and brittle hair, thin eyebrows and dry skin was recently reported to have c.897_898delTG, predicting p.(Cys299*) in RNF113A and we provide additional clinical details for this patient. This report further supports deleterious variants in RNF113A as a cause of a novel trichothiodystrophy syndrome.     

Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states

Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant trait characterized by tumors of the parathyroids, gastro- intestinal endocrine tissue, anterior pituitary and other tissues. We recently cloned the MEN1 gene and confirmed its identity by finding mutations in FMEN1. We have now extended our mutation analysis to 34 more unrelated FMEN1 probands and to two related states, sporadic MEN1 and familial hyperparathyroidism. There was a high prevalence of heterozygous germline MEN1 mutations in sporadic MEN1 (8/11 cases) and in FMEN1 (47/50 probands). One case of sporadic MEN1 was proven to be a new MEN1 mutation. Eight different mutations were observed more than once in FMEN1. Forty different mutations (32 FMEN1 and eight sporadic MEN1) were distributed across the MEN1 gene. Most predicted loss of function of the encoded menin protein, supporting the prediction that MEN1 is a tumor suppressor gene. No MEN1 germline mutation was found in five probands with familial hyperparathyroidism, suggesting that familial hyperparathyroidism often is caused by mutation in another gene or gene(s).