Microduplication of 15q13.3 and Xq21.31 in a family with tourette syndrome and comorbidities

Tourette syndrome (TS) is a childhood onset neurodevelopmental disorder. Although it is widely accepted that genetic factors play a significant role in TS pathogenesis the etiology of this disorder is largely unknown. Identification of rare copy number variations (CNVs) as susceptibility factors in several neuropsychiatric disorders such as attention deficit‐hyperactivity disorder (ADHD), autism and schizophrenia, suggests involvement of these rare structural changes also in TS etiology. In a male patient with TS, ADHD, and OCD (obsessive compulsive disorder) we identified two microduplications (at 15q13.3 and Xq21.31) inherited from a mother with subclinical ADHD. The 15q duplication included the CHRNA7 gene; while two genes, PABPC5 and PCDH11X, were within the Xq duplication. The Xq21.31 duplication was present in three brothers with TS including the proband, but not in an unaffected brother, whereas the 15q duplication was present only in the proband and his mother. The structural variations observed in this family may contribute to the observed symptoms, but further studies are necessary to investigate the possible involvement of the described variations in the TS etiology. © 2013 Wiley Periodicals, Inc.     

An unusual case of fatty liver in a patient with desmoid tumor

A desmoid tumor, also known as aggressive fibromatosis, is a rare benign neoplasm that arises from fascial or musculoaponeurotic tissues. It can occur in any anatomical location, most commonly the abdominal wall, shoulder girdle and retroperitoneum. The typical clinical presentation is a painless mass with a slow and progressive invasion of contiguous structures. It is associated with a high local recurrence rate after resection. Many issues regarding the optimal treatment of desmoid tumors remain controversial. Aggressive surgical resection with a wide margin (2-3 cm) remains the gold standard treatment with regard to preserving quality of life. Radiotherapy alone has been shown to be effective for the control of unresectable or recurrent lesions. Desmoid tumors tend to be locally infiltrative, therefore, the fields must be generous to prevent marginal recurrence. The radiation dose appropriate for treating desmoid tumors remains controversial. We present a 25-year-old Caucasian man with local recurrence of a desmoid tumor after repeated surgical resection, treated with radiotherapy. The patient achieved complete tumor regression at 4 mo after radiotherapy, and he is clinically free of disease at 12 mo after the end of treatment, with an acceptable quality of life. The patient developed short bowel syndrome as a complication of second surgical resection. Consequently, radiotherapy might have worsened an already present malabsorption and so led to steatohepatitis.     

Evaluation of 24-locus MIRU-VNTR in extrapulmonary specimens: study from a tertiary centre in Mumbai

Genotyping of Mycobacterium tuberculosis isolates is a useful tool for epidemiological control of tuberculosis (TB) and phylogenetic exploration of the pathogen. There is a lack of information on the discriminatory power of standard 24-locus mycobacterial interspersed repetitive unit (MIRU) - variable number tandem repeats (VNTR) in India, which has the highest tuberculosis (TB) burden worldwide. Therefore, we assessed its utility on 69 M.?tuberculosis (MTB) isolates from patients with extrapulmonary tuberculosis, in comparison to standard insertion sequence (IS) 6110-Restriction fragment length polymorphism (RFLP) fingerprinting and spoligotyping. IS6110-RFLP (HGDI, 0.9987) identified a single cluster of 3 (4.3%) single-copy IS6110 isolates. Spoligotyping showed 69.5% clustering (HGDI, 0.8857). In contrast, MIRU-VNTR analysis identified 69 (100%) unique strains (HGDI, 1.0000). Within the study limits, this observed high discriminatory power suggests that 24-locus MIRU-VNTR genotyping could potentially be used to study long-term transmission of MTB infection in Mumbai. Moreover, high congruence between the MIRU-VNTR-based and spoligotyping-based strain groupings suggests that CAS, EAI and Beijing are the predominant strain lineages in the Mumbai TB patient population. The Beijing lineage isolates were found to be more significantly associated with multi-drug resistance (p?相似文献   

Multiplex allele specific PCR for rapid detection of extensively drug resistant tuberculosis

Effective tuberculosis (TB) control is hindered by lack of rapid diagnostic tests for detection of drug-resistant TB (DR-TB). Use of molecular tools for rapid detection of multi-and extensively- DR-TB, could facilitate early initiation of appropriate anti-tubercular treatment (ATT) regimen thereby interrupting transmission. Understanding the urgent situation, we standardized and evaluated 4 individual multiplex allele specific PCR (MAS-PCR) assays on 450 sputum specimens for Mycobacterium tuberculosis (MTB) detection and determination of drug resistance by targeting katG315, rpoB531, gyrA 94, rrs 1401 codon mutations for determination of resistance to Isoniazid (INH), Rifampicin (RIF), Fluoroquinolones (FQ) and Aminoglycosides (AG) respectively. Using a single sputum specimen, MAS-PCR correctly identified 97.2% (281/289; 95% CI:95-99) culture positive patients as MTB positive, 100% (271/271; 95% CI:99-100) for smear positive cases and 55.5% (10/18; 95% CI:34-75) for smear negative cases; and correctly identified 93.6% (104/111; 95% CI:87-97) of culture negative patients. Individual MAS-PCR assays reported variable diagnostic accuracy for determination of drug resistance. On comparison with phenotypic drug susceptibility testing, MAS-PCR assays correctly identified 89.2% (191/214; 95% CI:84-93), 94.9% (187/197; 95% CI:91-97), 72.5% (98/135; 95% CI:65-79) and 92.3% (24/26; 95% CI:75-99) of INH resistant, RIF resistant, FQ resistant and AG resistant specimens respectively; and correctly identified 94% (63/67; 95% CI:85-98), 86.9% (73/84; 95% CI:78-93), 93.1% (136/146; 95% CI:88-96) and 99.2% (253/255; 95% CI:97-100) of INH sensitive, RIF sensitive, FQ sensitive and AG sensitive specimens respectively. Thus, use of MAS-PCR assays for rapid detection of DR-TB is recommended, enabling early initiation of appropriate ATT.     

Biomimetic synthesis of galantamine via laccase/TEMPO mediated oxidative coupling

Laccase-mediated intramolecular oxidative radical coupling of N-formyl-2-bromo-O-methylnorbelladine afforded a novel and isolable spirocyclohexadienonic intermediate of galantamine. High yield and conversion of substrate were obtained in the presence of the redox mediator 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). This laccase procedure, with an overall yield of 34%, represents a scalable and environmentally friendly alternative to previously reported syntheses of galantamine based on the use of potassium ferricyanide as an unspecific radical coupling reagent.

Laccase-mediated intramolecular oxidative radical coupling of N-formyl-2-bromo-O-methylnorbelladine afforded a novel and isolable spirocyclohexadienonic intermediate of galantamine.     

The rational of forehead lifting in patients with chronic facial paralysis

Background

The incidence of permanent facial sequels in patients with Bell’s palsy is about 30 % and results in impaired mimic expression of both midface and forehead in varying degrees. Even at rest, most patients experience an imbalance of their facial features. In this article, static correction of brow imbalance was evaluated in patients with sequels after unilateral facial palsy.

Methods

Thirty-one patients with sequels of Bell’s palsy underwent surgery with endoscopic forehead lift. Brow position was geometrically assessed pre- and postoperatively. The validated self-assessment instrument for quality of life [Short Form 36(SF-36)] was completed prior to and after surgery. The follow-up period was 12 months.

Results

A notable improvement in the position of the brows was demonstrated over time with lasting results. All patients experienced an improvement in facial symmetry and balance at rest. However, no significant difference could be shown using SF-36 pre- and postoperatively.

Conclusion

Endoscopic forehead lift combined or as an isolated procedure is a valuable instrument to correct sequels of Bell’s palsy. Level of Evidence: Level IV, therapeutic study.     

Reactive Tonsillar Enlargement Showing Strong 18F-Fdg Uptake During the Follow-Up of Follicular Lymphoma

The ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a standard procedure for the diagnosis, staging, and restaging in lymphoma patients. However, a relative high rate of false-positive results has been reported. We report a case of a 40-year-old man with a previous history of a nodal follicular lymphoma, stage IVA, treated with R-CHOP, which showed strong ¹⁸F-FDG uptake in the Waldeyer’s tonsillar ring during his follow-up, being considered highly suspicious of relapsed lymphoma. A surgical removal of the palatine tonsils and adenoids was performed, which showed reactive follicular hyperplasia. Furthermore, bone marrow biopsy revealed absence of neoplasia. The patient is still in follow-up with no signs of recurrent lymphoma. This case illustrates that, despite the high sensitivity for the detection of recurrent lymphoma, ¹⁸F-FDG uptake should be interpreted with great caution and confirmatory studies should be performed before any therapy.