Search PubMed⌕ Search

Biomedical subjects

Daljit Singh

Publications and source records attributed to Daljit Singh.

At least 19 recordsLinked to original sources
PubMed2006

A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin.

PURPOSE: To identify the genetic defect in an autosomal dominant congenital cataract family, having 15 members in three generations, affected with bilateral cataract that gave the appearance of "full moon" with Y-sutural opacities. METHODS: A detailed family history and clinical data were recorded. A genome-wide scan by two point linkage analysis using nearly 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was carried out. Mutation screening was performed in the candidate gene by bidirectional sequencing of amplified products. RESULTS: A maximum two point lod score of 5.45 at theta=0.00 was obtained with marker D1S534. Haplotype analysis placed the cataract locus to a 14.1 cM region between D1S221 and D1S498, in close proximity to the gene for the gap junction channel protein connexin 50 (GJA8) at 1q21. Mutation screening in GJA8 identified a novel G>C transversion at nucleotide position c.235. This nucleotide change resulted in the substitution of highly conserved valine by leucine at codon 79 (V79L). This nucleotide substitution was neither seen in any unaffected member of the family nor in 180 unrelated control subjects (360 chromosomes) from same ethnic background tested by sequence analysis of GJA8. CONCLUSIONS: The present study describes the mapping of a locus for congenital cataract that appeared like "full moon" with Y-sutural opacities at 1q21 and identifies a previously unreported mutation in GJA8. These findings thus expand the mutation spectrum of GJA8.

Asian People↗
PubMed2006

Pathological laughter in trigeminal schwannoma: case report and review of the literature.

Pathological laughter is an uncommon manifestation of neurosurgical diseases. Very few cases of trigeminal schwannoma have been reported in the literature presenting with pathological laughter as a predominant symptom. We are reporting on a case of multi-compartmental trigeminal schwannoma presenting as pathological laughter and discuss a review of the literature. A 23-year-old lady presented with pathological laughter, along with symptoms pertaining to other cranial nerves and cerebellar dysfunction. Magnetic resonance imaging (MRI) of the brain was suggestive of a dumbbell-shaped mass in the middle and posterior cranial fossa on the left side, causing significant compression of the pons. She was investigated and operated for multi-compartmental trigeminal schwannoma. Following surgery, abnormal laughter disappeared immediately and no recurrence of symptoms was -present for a follow-up of 16 months. This case supports the role of the brainstem, especially the pons, in the control of laughter and, perhaps, of the medial temporal lobe too.

Adult↗
PubMed2006

A novel fan-shaped cataract-microcornea syndrome caused by a mutation of CRYAA in an Indian family.

PURPOSE: The molecular characterization of an Indian family having 10 members in four generations affected with a unique fan-shaped cataract-microcornea syndrome. METHODS: Detailed family history and clinical data were recorded. A genome-wide screening by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was carried out. Mutation screening was performed in the candidate gene by bi-directional sequencing of amplified products. RESULTS: The cataract-microcornea locus in this family was mapped to a 23.5 cM region on chromosome 21q22.3. Direct sequencing of the candidate gene CRYAA revealed a heterozygous C>T transition resulting in the substitution of the highly conserved arginine at position 116 by cysteine (R116C). CONCLUSIONS: This study provides the report of mapping a locus for syndromal cataract (cataract-microcornea syndrome) on 21q22.3. The mutation observed in CRYAA in the present family highlights the phenotypic heterogeneity of the disorder in relation to the genotype, as an identical mutation has previously been reported in an American family with a different type of cataract. The "fan-shaped cataract" observed in the present family has not been reported before.

Asian People↗
PubMed2006

A novel mutation in the DNA-binding domain of MAF at 16q23.1 associated with autosomal dominant "cerulean cataract" in an Indian family.

Congenital cataract, a clinically and genetically highly heterogeneous eye disorder, is one of the significant causes of visual impairment or blindness in children. It is frequently inherited as an autosomal dominant trait. We investigated a three-generation family of Indian origin with 12 members affected with cerulean cataract. Linkage analysis was carried out in this family using more than 100 microsatellite markers for the known cataract candidate gene loci. A positive two-point lod score of 3.9 at theta = 0.000, indicative of linkage, was obtained with three microsatellite markers for chromosome 16. Multipoint and haplotype analysis narrowed the cataract locus to a 15.3 cM region between markers D16S518 and D16S511 that corresponds to the region 16q23.1. Direct sequencing of the candidate gene MAF, which lies in the critical linked region, revealed a novel heterozygous missense mutation in the basic region (BR) of the DNA-binding domain. This sequence change was considered pathogenic as it segregated in all affected family members, neither seen in unaffected family members nor in 106 unrelated controls. The mutation also results in substitution of highly conserved lysine 297 by arginine (K297R) that affects a residue that forms a part of a predicted DNA-interaction region of the protein. The association of microcornea with congenital cataract in some affected individuals further underlines the role of the MAF transcription factor in lens and anterior ocular development. Our findings expand the mutation spectrum of MAF in association with congenital cataract and highlight the genetic and phenotypic heterogeneity of congenital cataract.

Adolescent↗
PubMed2006

Sutural cataract associated with a mutation in the ferritin light chain gene (FTL) in a family of Indian origin.

PURPOSE: The molecular characterization of 27 members of an Indian family, with 13 members in four generations, affected with Y-sutural congenital cataract. METHODS: Detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was performed. Mutation screening was carried out in the candidate gene by bi-directional sequencing of amplified products. RESULTS: A maximum two-point lod score of 6.37 at theta=0.00 was obtained with marker D19S879. Haplotype analysis placed the cataract locus to a 5.0 cM region between D19S902 and D19S867, in close proximity to the L-ferritin light chain gene (FTL) on chromosome 19q13.3. Hematological tests in two affected individuals showed very high levels of serum ferritin without iron overload leading to the diagnosis of hyperferritinemia-cataract syndrome. Mutation screening in FTL identified a G>A change at position 32 (c.-168G>A) in a highly conserved 3 nucleotide motif that forms a loop structure in the iron responsive element (IRE) in the 5'-untranslated region (5'-UTR). This nucleotide alteration was neither seen in any unaffected member of the family nor found in 50 unrelated control subjects. CONCLUSIONS: The present study is the first report of a Y-sutural congenital cataract mapping to 19q13.3. The mutation observed in FTL in this family highlights the phenotypic heterogeneity of the disorder in relation to the genotype as the identical mutation (32 G>A) has previously been reported in two Italian families with entirely different phenotypes. It is also the first report of hereditary hyperferritinemia-cataract syndrome in a family of Indian origin.

5' Untranslated Regions↗
PubMed2006

Histological analysis of lesions of the pineal region: a retrospective study of 12 years.

Various types of tumors and non-tumor lesions arise in the pineal region. This study summarizes the experience the authors have gained with 54 lesions of the pineal region over the last 12 years. Histology was analyzed in all cases. Out of these 54 cases, four were non-tumor lesions. Of the 50 tumors, pineal parenchymal tumors (PPTs) were most common (42% (21/54)), followed by gliomas (40% (20/54)). The PPTs were pineoblastomas (10/21), PPT of intermediate differentiation (7/21), and pineocytomas (4/21). The other tumors included germ cell tumors (4/54), meningiomas (2/54), craniopharyngiomas (2/54), and choroid plexus papilloma (1/54). The non-tumor lesions were epidermoid cysts (2/54), tuberculous abscess (1/54), and cysticercosis (1/54). Immunohistochemically, all the PPTs showed cytoplasmic positivity for synaptophysin. Glial fibrillary acidic protein (GFAP) stained only the reactive astrocytes in these tumors except two cases of pineoblastoma, which showed GFAP positivity in some tumor cells, indicating glial differentiation. There are very few studies of pineal lesions, and there is no study from India in the indexed literature.

Adolescent↗
PubMed2006

Ablation pit treatment for corneal decompensation.

Historically, the management of cloudy, decompensated corneas centered around replacement of corneal tissue with either a through-and-through or partial-thickness replacement. This article presents a technique that is a radical departure from prior methods.

Aged, 80 and over↗
PubMed2006

A clinical profile of shock in children in Punjab, India.

This prospective study was conducted to determine the frequency, etiology, type and outcome of shock in hospitalized children in the age group of 1 month to 15 years. There were 98 cases of shock, constituting 4.3% out of total admissions. Mean age was 2.8 +/-3.4 years. Maximum number of patients (39) was seen in infancy. Hypovolemic shock due to acute diarrheal disease was the commonest type (45.9%) followed by septic, cardiogenic and distributive shock. Compensated stage was common in hypovolemic shock (88.9%) whereas majority of patients with septic shock (73.5%) presented in decompensated stage. Overall survival was 73.6%. The survival rate was best in hypovolemic shock (97.7%;) followed by septic(53.3%) and cardiogenic shock(43.7%). Inotropes and ventilatory support were required in 46% and 23% patients, respectively. Diagnosis and management of shock in compensated stage carried better prognosis than in uncompensated shock irrespective of the age of the patient.

Adolescent↗
PubMed2005

Clinical and anthropometric profile of children with celiac disease in Punjab (North India).

This prospective study was carried out to evaluate the clinical and anthropometric profile of 71 children confirmed to have celiac disease on the basis of clinical features, duodenal biopsy and unequivocal improvement on gluten-free diet. Serological tests were performed in 35 cases. The patients were divided into three age groups <5 years, 5-10 years, and >10 years as per the age of presentation to the hospital. Mean age was 8.7 years with a slight female preponderance. Diarrhea was the commonest presentation in group I and failure to thrive in group III. All patients in group III, had weight for age (w/a) <3rd percentile and majority (83 per cent) had short stature, with delayed puberty in all. All children had significant improvement in symptoms and growth on gluten restriction. None of the patients had been suspected to have celiac disease before, which signifies that in spite of increasing incidence of celiac disease, this disease is grossly under-diagnosed in North India where wheat is the staple diet. It is essential to make an early diagnosis of celiac disease in children to prevent growth delay.

Adolescent↗
PubMed2005

Recurrent tumefactive demyelination in a child.

A 13-year-old female presented with two episodes of hemiplegia and hemianopia involving opposite sides, each time associated with seizures. On both occasions, the magnetic resonance (MR) scan showed a giant demyelinating, peripherally enhancing lesion with mass effect. MR spectroscopy (MRS) was indistinguishable from a tumor. At the first episode, she had undergone tumor decompression but the histopathology revealed an acute demyelinating lesion with no evidence of tumor. Each time there was partial clinical recovery and resolution of the radiological lesion, the patient having received corticosteroids during both of the episodes. She also developed hemiballismus postoperatively which resolved on withdrawing phenytoin. It is suggested that a trial of corticosteroids be given in suspected tumefactive demyelinating lesions, although they may be indistinguishable from a tumor.

Adolescent↗
PubMed2005

A randomized controlled trial of phenobarbital in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: Phenobarbital is one of the oldest, cheapest and most easily available cerebro-protective drugs for the hypoxic brain. It has multiple actions that could be of benefit to the asphyxiated brain. However, its potential has not been fully explored. OBJECTIVE: To study the effect of phenobarbital given within six hours of life to term and near-term asphyxiated neonates, on mortality, neurological abnormality at discharge and seizures. METHODS: This was a randomized controlled trial set in a tertiary care referral perinatal centre. Asphyxiated neonates (gestational age >or= 34 weeks) manifesting with hypoxic ischemic encephalopathy (HIE) in the first six hours of life were randomized to receive either injection of phenobarbital 20 mg/kg IV or to the control group. The primary outcome was death or abnormal neurological examination at discharge while seizures, need for ventilation and multi-organ dysfunction were secondary outcomes. RESULTS: Twenty-five babies received phenobarbital and 20 were in the control group. The mortality (20% vs. 15%) and abnormal neurological outcome at discharge (30% vs. 53%, p = 0.15) were statistically not different between the two groups. In the phenobarbital group, 8% of neonates developed seizures while 40% of babies in the control group developed seizures (p = 0.01, relative risk (RR) = 0.20 (0.05-0.84)). Phenobarbital was well tolerated and did not increase the need for respiratory support. CONCLUSIONS: Phenobarbital in the dose of 20 mg/kg IV given within six hours of life to term and near-term neonates with HIE, significantly decreased the incidence of neonatal seizures and was well tolerated. However, it did not alter the mortality and neurologic outcome at discharge.

Anticonvulsants↗
PubMed2004

Effect of phenobarbital on free radicals in neonates with hypoxic ischemic encephalopathy--a randomized controlled trial.

BACKGROUND: Phenobarbital is one of the oldest, cheapest and easily available cerebroprotective drugs for the hypoxic brain. However, its potential and various actions have not been fully explored. AIM: To evaluate the effects of Phenobarbital on levels of oxidants and anti-oxidants in term and near term neonates with hypoxic ischemic encephalopathy. METHODS: Design--randomized controlled trial. Setting--tertiary care referral perinatal centre. Procedure--asphyxiated neonates (gestation > or = 34 weeks) with HIE were randomized to receive Phenobarbital 20 mg/kg i.v. within first six hours of life or to control group. CSF levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and blood levels of vitamins A and E were estimated at 10-12 hours of age. RESULTS: CSF levels of MDA, SOD, GPx and blood levels of vitamins A and E were significantly lower in the Phenobarbital group (p<0.001). There was a trend towards lower levels of CSF MDA, SOD, GPx and blood vitamins A and E in babies with normal outcome as compared to babies with adverse outcome (death or neurologically abnormal at discharge). CONCLUSION: Phenobarbital in the dose of 20 mg/kg i.v. given within 6 hours of life in term and near-term neonates with HIE, was associated with a decrease in lipid peroxides, anti-oxidant enzymes and anti-oxidant vitamins.

Anticonvulsants↗
PubMed2003

R5 retrotransposons insert into a family of infrequently transcribed 28S rRNA genes of planaria.

A small (100 bp) region of the 28S rRNA gene has been shown to serve as the target site for the insertion of non-long terminal repeat (non-LTR) retrotransposons in both arthropods and nematodes. Here we characterize a lineage of non-LTR retrotransposons that inserts into this target site in the phylum Platyhelminthes. Dugesiid planaria contain elements, named R5, that insert 8 bp upstream of the target site used by arthropod R2 elements. The complete sequence of this element from Girardia tigrina revealed that it encoded two open reading frames (ORFs). The second ORF contained reverse transcriptase and restriction enzyme-like endonuclease domains similar to those found in R2 and R4, the elements that insert into the 28S genes of nematodes. The closest relative of R5, however, was the element NeSL-1, which inserts into the spliced leader 1 exons of nematodes. The rRNA genes of dugesiid planaria are unusual in that they comprise two types of rDNA units that differ by 8%-10% in nucleotide sequence of the 18S and 28S coding regions. Type II units are transcribed in adult tissues at levels that are less than 1% that of the type I units. R5 elements were only found inserted in the type II units, where presumably they cause less harm to the host. A second unusual aspect of the dugesiid rRNA genes is that the target site for the R5 insertion is duplicated 300 bp upstream of the original insertion site. R5 elements were identified at both sites. These findings expand the distribution of non-LTR elements that are specialized for insertion into the 28S gene and suggest that still more elements exist in other eukaryotic taxa. Attempts to trace the phylogeny of R5 did not offer sufficient resolution to determine whether R2, R4, and R5 represent the same lineage or whether they represent independent specializations for the 28S gene.

Animals↗
PubMed2003

Surgical management and outcome of tuberculous atlantoaxial dislocation: a 15-year experience.

OBJECTIVE: Tuberculous atlantoaxial dislocation is a rare disease entity. However, tuberculosis continues to be endemic in developing countries. Its earliest clinical presentation may be nonspecific, and delay in diagnosis may lead to irreversible neurological deficit. The management of tuberculous atlantoaxial dislocation includes ventral cervicomedullary decompression, occipitocervical arthrodesis, and administration of antituberculous medications. METHODS: Eighteen patients with tuberculous atlantoaxial dislocation who presented with neck pain and/or occipital headache, restriction of neck movement, difficulty swallowing, and signs of myelopathy were studied. Four patients had evidence of associated pulmonary tuberculosis. Plain x-rays of the cervical spine, computed tomographic scans, and magnetic resonance images were obtained in all patients for diagnosis and to assess the degree of dislocation and cervicomedullary compression. Simultaneous anterior neural decompression, via a transcervical retropharyngeal approach, and posterior arthrodesis were performed on all patients while they remained under anesthesia. Antituberculous chemotherapy was continued for 18 months. RESULTS: Histopathological analysis of excised tissue was consistent with tuberculosis in all patients. However, Ziehl-Neelsen staining for acid-fast bacilli was positive in two cases, and culture for Mycobacterium tuberculosis was negative in all patients. Patients with severe myelopathy experienced marked improvement. One patient died of fulminant resistant tuberculous meningitis. CONCLUSION: The transcervical retropharyngeal approach to the craniovertebral junction provides direct access to the lesion and avoids the potential bacterial contamination of the oral and pharyngeal cavity. It also prevents the development of persistent fistulae. Posterior stabilization should be performed directly after anterior neural decompression, while the patient remains under anesthesia, to prevent neurological deterioration before subsequent posterior fixation. This technique also is helpful for early mobilization of patients. The aim of surgical treatment should be to obtain biopsy tissue and to perform radical excision of epidural granulation tissue/abscess and infected bone using microsurgical technique. Antituberculous medication must be continued for 18 months with four drug regimens, and continuous monitoring of drug toxicity should be performed throughout the course of treatment.

Adolescent↗