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ABSTRACT We report a 2.2 year-old-boy, born of consanguineous marriage, referred for short stature, with history of neonatal death and skeletal deformities in his older sibling. Rhizo-mesomelic dwarfism was detected antenatally. Within 24 hours of birth, he developed multiple seizures. Examination revealed severe short stature, dolichocephaly, broad forehead, deep set eyes, low set ears, bulbous nose, small, irregular teeth, pointed chin, and triangular facies. He had rhizomelic shortening, stubby fingers, pes planus, and scanty hair. Neurological evaluation revealed ataxia, hypotonia, and global developmental delay. Skeletal survey radiograph revealed shallow acetabuli, short femurs and humerus, short, broad metacarpals and short cone-shaped phalanges with cupping of phalangeal bases. Clinical exome analysis revealed homozygous mutations involving the POC1A gene and the SLC13A5 gene responsible for SOFT syndrome and Kohlschutter-Tonz syndrome respectively, which were inherited from the parents. Both these syndromes are extremely rare, and their co-occurrence is being reported for the first time.

Introduction: The association of pulmonary hemosiderosis with celiac disease (Lane-Hamilton syndrome) is extremely rare. Case Details: A five-year-old female child presented with fever, cough, breathlessness, and pallor for 20 days, without any previous history of recurrent lower respiratory tract infections, tuberculosis, or cardiac disease. There was no history of pica, chronic diarrhea, bleeding, or personal or family history of repeated blood transfusions. She had tachycardia, tachypnea, severe pallor, stunting, rickets, and bilateral fine lung crepitations. Peripheral smear and blood indices revealed dimorphic anemia. Anti-tissue transglutaminase IgA antibody levels were high (>200 U/mL) and the upper gastrointestinal endoscopy with duodenal biopsy confirmed the diagnosis of celiac disease. The child was discharged on a gluten-free diet (GFD) and oral hematinic, but her dietary compliance was poor. Interestingly, the child had persistent bilateral pulmonary infiltrates, which was initially attributed to congestive cardiac failure (CCF), which persisted even despite treatment. HRCT chest revealed interstitial thickening and bilateral alveolar shadows and bronchoalveolar lavage showed a few inflammatory cells. The child was readmitted four times with similar complaints and was given packed red cell transfusions. In the fourth admission, a lung biopsy was done, which revealed extensive pulmonary hemosiderosis. The patient was given a course of oral steroids for 6 weeks, with a gluten-free diet, following which both the anemia and the pulmonary infiltrates resolved. Conclusion: Pulmonary hemosiderosis is an important cause of anemia in cases of celiac disease and may be misdiagnosed as CCF due to severe anemia. A strict GFD, with or without corticosteroids, can reverse the clinical and radiological picture.

Gene therapy aims to revert diseased phenotypes by the use of both viral and nonviral gene delivery systems. Substantial progress has been made in making gene transfer vehicles more efficient, less toxic, and nonimmunogenic and in allowing long-term transgene expression. One of the key issues in successfully implementing gene therapies in the clinical setting is to be able to regulate gene expression very tightly and consistently as and when it is needed. The regulation ought to be achievable using a compound that should be nontoxic, be able to penetrate into the desired target tissue or organ, and have a half-life of a few hours (as opposed to minutes or days) so that when withdrawn or added (depending on the regulatable system used) gene expression can be turned \"on\" or \"off\" quickly and effectively. Also, the genetic switches employed should ideally be nonimmunogenic in the host. The ability to switch transgenes on and off would be of paramount importance not only when the therapy is no longer needed, but also in the case of the development of adverse side effects to the therapy. Many regulatable systems are currently under development and some, i.e., the tetracycline-dependent transcriptional switch, have been used successfully for in vivo preclinical applications. Despite this, there are no examples of switches that have been employed in a human clinical trial. In this review, we aim to highlight the main regulatable systems currently under development, the gene transfer systems employed for their expression, and also the preclinical models in which they have been used successfully. We also discuss the substantial challenges that still remain before these regulatable switches can be employed in the clinical setting.