ABSTRACT
BACKGROUND: Anaplastic large cell lymphoma (ALCL) is an uncommon T-cell lymphoma, accounting for 10-15% of pediatric non-Hodgkin lymphoma (NHL). Outcomes of ALCL have not improved in recent years despite better chemotherapy and supportive care. This study aimed to analyze the clinical profile and outcomes of pediatric ALCL patients at our center. MATERIALS AND METHODS: Medical records of children with ALCL from July 2017 to December 2019 were reviewed. Their clinical and laboratory details were noted. The outcomes of all patients were recorded. RESULTS: Ten patients were diagnosed with ALCL during this period. The median age at diagnosis was 8 years, with 7 patients being boys. Lymph nodes were the primary site of involvement in four children. Extranodal involvement was seen in 60%. One patient had the underlying chronic granulomatous disease (CGD). Systemic (B) symptoms were seen in 70%. Three children had hemophagocytic lymphohistiocytosis (HLH) at presentation. All of them had stage-III disease. Seven patients were treated on the Berlin-Frankfurt-Münster-non-Hodgkin lymphomas (BFM-NHL) 90 protocol and three children are currently in remission. Four patients had disease relapse/progressive disease while on therapy. Three children had HLH at presentation and all had poor outcomes. CONCLUSIONS: Pediatric ALCL has diverse and atypical clinical presentation and a high index of suspicion is needed for diagnosis. ALCL is an aggressive malignancy and is responsive to multiagent chemotherapy, though survival has not improved over the past decade. The integration of novel agents may improve the outcome.
ABSTRACT
Abstract The present study describes the haematological profile, feeding preference, and comparison of morphometric characters of blue rock pigeon (Columba livia) breeding pairs. For this purpose, 25 pairs (25 samples per sex) were sampled through Mist nets from district Okara and Bahawalnagar, Punjab, Pakistan. Birds were then anaesthetized with a combination of ketamine HCL (10 mg/kg) and diazepam (0.2 mg/kg) and subjected to morphometric measurements. 5µL blood also was taken from the jugular vein of each anaesthetized bird for haematological analysis. Few pairs were also dissected to remove gastrointestinal tracts (GITs) for food preferences. Results revealed that there are no significant differences in the haematological parameters and feeding preference of breeding pairs of Columba livia. The gut analysis further revealed, the major portion of gut contents consisted of pea and corn in most of the pairs. Regarding the mensural measurements, significant differences were recorded in the body weight, length of the longest primary feather, and chest circumference, whereas the rest of the studied parameters remain nonsignificant between sexes. So, it is concluded that apart from 3 morphometric parameters (body weight, length of longest primary feather and chest circumference), both sexes are alike in term of morphometry, haematology and food preference.
Resumo O presente estudo descreve o perfil hematológico, a preferência alimentar e a comparação de caracteres morfométricos de casais reprodutores de pombo-rocha (Columba livia). Para tanto, 25 pares (25 amostras por sexo) foram amostrados por meio de redes de névoa do distrito de Okara e Bahawalnagar, Punjab, Paquistão. As aves foram então anestesiadas com uma combinação de cetamina HCL (10 mg/kg) e diazepam (0,2 mg/kg) e submetidas a medidas morfométricas; 5 µL de sangue também foram retirados da veia jugular de cada ave anestesiada para análise hematológica. Poucos pares também foram dissecados para remover o trato gastrointestinal (GITs) para preferências alimentares. Os resultados revelaram que não há diferenças significativas nos parâmetros hematológicos e na preferência alimentar dos casais reprodutores de Columba livia. A análise intestinal revelou ainda que a maior parte do conteúdo intestinal consistia em ervilha e milho na maioria dos pares. Em relação às medidas mensurais, foram registradas diferenças significativas no peso corporal, comprimento da pena primária mais longa e circunferência torácica, enquanto os demais parâmetros estudados permanecem não significativos entre os sexos. Assim, conclui-se que além de três parâmetros morfométricos (peso corporal, comprimento da pena primária mais longa e circunferência torácica), ambos os sexos são semelhantes em termos de morfometria, hematologia e preferência alimentar.
Subject(s)
Animals , Columbidae , Food Preferences , Pakistan , Feathers , Plant BreedingABSTRACT
The present study describes the haematological profile, feeding preference, and comparison of morphometric characters of blue rock pigeon (Columba livia) breeding pairs. For this purpose, 25 pairs (25 samples per sex) were sampled through Mist nets from district Okara and Bahawalnagar, Punjab, Pakistan. Birds were then anaesthetized with a combination of ketamine HCL (10 mg/kg) and diazepam (0.2 mg/kg) and subjected to morphometric measurements. 5µL blood also was taken from the jugular vein of each anaesthetized bird for haematological analysis. Few pairs were also dissected to remove gastrointestinal tracts (GITs) for food preferences. Results revealed that there are no significant differences in the haematological parameters and feeding preference of breeding pairs of Columba livia. The gut analysis further revealed, the major portion of gut contents consisted of pea and corn in most of the pairs. Regarding the mensural measurements, significant differences were recorded in the body weight, length of the longest primary feather, and chest circumference, whereas the rest of the studied parameters remain nonsignificant between sexes. So, it is concluded that apart from 3 morphometric parameters (body weight, length of longest primary feather and chest circumference), both sexes are alike in term of morphometry, haematology and food preference.
O presente estudo descreve o perfil hematológico, a preferência alimentar e a comparação de caracteres morfométricos de casais reprodutores de pombo-rocha (Columba livia). Para tanto, 25 pares (25 amostras por sexo) foram amostrados por meio de redes de névoa do distrito de Okara e Bahawalnagar, Punjab, Paquistão. As aves foram então anestesiadas com uma combinação de cetamina HCL (10 mg/kg) e diazepam (0,2 mg/kg) e submetidas a medidas morfométricas; 5 µL de sangue também foram retirados da veia jugular de cada ave anestesiada para análise hematológica. Poucos pares também foram dissecados para remover o trato gastrointestinal (GITs) para preferências alimentares. Os resultados revelaram que não há diferenças significativas nos parâmetros hematológicos e na preferência alimentar dos casais reprodutores de Columba livia. A análise intestinal revelou ainda que a maior parte do conteúdo intestinal consistia em ervilha e milho na maioria dos pares. Em relação às medidas mensurais, foram registradas diferenças significativas no peso corporal, comprimento da pena primária mais longa e circunferência torácica, enquanto os demais parâmetros estudados permanecem não significativos entre os sexos. Assim, conclui-se que além de três parâmetros morfométricos (peso corporal, comprimento da pena primária mais longa e circunferência torácica), ambos os sexos são semelhantes em termos de morfometria, hematologia e preferência alimentar.
Subject(s)
Animals , Columbidae/anatomy & histology , Columbidae/blood , Diet/veterinaryABSTRACT
Abstract The present study describes the haematological profile, feeding preference, and comparison of morphometric characters of blue rock pigeon (Columba livia) breeding pairs. For this purpose, 25 pairs (25 samples per sex) were sampled through Mist nets from district Okara and Bahawalnagar, Punjab, Pakistan. Birds were then anaesthetized with a combination of ketamine HCL (10 mg/kg) and diazepam (0.2 mg/kg) and subjected to morphometric measurements. 5µL blood also was taken from the jugular vein of each anaesthetized bird for haematological analysis. Few pairs were also dissected to remove gastrointestinal tracts (GITs) for food preferences. Results revealed that there are no significant differences in the haematological parameters and feeding preference of breeding pairs of Columba livia. The gut analysis further revealed, the major portion of gut contents consisted of pea and corn in most of the pairs. Regarding the mensural measurements, significant differences were recorded in the body weight, length of the longest primary feather, and chest circumference, whereas the rest of the studied parameters remain nonsignificant between sexes. So, it is concluded that apart from 3 morphometric parameters (body weight, length of longest primary feather and chest circumference), both sexes are alike in term of morphometry, haematology and food preference.
Resumo O presente estudo descreve o perfil hematológico, a preferência alimentar e a comparação de caracteres morfométricos de casais reprodutores de pombo-rocha (Columba livia). Para tanto, 25 pares (25 amostras por sexo) foram amostrados por meio de redes de névoa do distrito de Okara e Bahawalnagar, Punjab, Paquistão. As aves foram então anestesiadas com uma combinação de cetamina HCL (10 mg/kg) e diazepam (0,2 mg/kg) e submetidas a medidas morfométricas; 5 µL de sangue também foram retirados da veia jugular de cada ave anestesiada para análise hematológica. Poucos pares também foram dissecados para remover o trato gastrointestinal (GITs) para preferências alimentares. Os resultados revelaram que não há diferenças significativas nos parâmetros hematológicos e na preferência alimentar dos casais reprodutores de Columba livia. A análise intestinal revelou ainda que a maior parte do conteúdo intestinal consistia em ervilha e milho na maioria dos pares. Em relação às medidas mensurais, foram registradas diferenças significativas no peso corporal, comprimento da pena primária mais longa e circunferência torácica, enquanto os demais parâmetros estudados permanecem não significativos entre os sexos. Assim, conclui-se que além de três parâmetros morfométricos (peso corporal, comprimento da pena primária mais longa e circunferência torácica), ambos os sexos são semelhantes em termos de morfometria, hematologia e preferência alimentar.
ABSTRACT
Diabetic Retinopathy (DR) is one of the leading causes of blindness for people who have diabetes in the world. However, early detection of this disease can essentially decrease its effects on the patient. The recent breakthroughs in technologies, including the use of smart health systems based on Artificial intelligence, IoT and Blockchain are trying to improve the early diagnosis and treatment of diabetic retinopathy. In this study, we presented an AI-based smart teleopthalmology application for diagnosis of diabetic retinopathy. The app has the ability to facilitate the analyses of eye fundus images via deep learning from the Kaggle database using Tensor Flow mathematical library. The app would be useful in promoting mHealth and timely treatment of diabetic retinopathy by clinicians. With the AI-based application presented in this paper, patients can easily get supports and physicians and researchers can also mine or predict data on diabetic retinopathy and reports generated could assist doctors to determine the level of severity of the disease among the people.
ABSTRACT
The present study describes the haematological profile, feeding preference, and comparison of morphometric characters of blue rock pigeon (Columba livia) breeding pairs. For this purpose, 25 pairs (25 samples per sex) were sampled through Mist nets from district Okara and Bahawalnagar, Punjab, Pakistan. Birds were then anaesthetized with a combination of ketamine HCL (10 mg/kg) and diazepam (0.2 mg/kg) and subjected to morphometric measurements. 5µL blood also was taken from the jugular vein of each anaesthetized bird for haematological analysis. Few pairs were also dissected to remove gastrointestinal tracts (GITs) for food preferences. Results revealed that there are no significant differences in the haematological parameters and feeding preference of breeding pairs of Columba livia. The gut analysis further revealed, the major portion of gut contents consisted of pea and corn in most of the pairs. Regarding the mensural measurements, significant differences were recorded in the body weight, length of the longest primary feather, and chest circumference, whereas the rest of the studied parameters remain nonsignificant between sexes. So, it is concluded that apart from 3 morphometric parameters (body weight, length of longest primary feather and chest circumference), both sexes are alike in term of morphometry, haematology and food preference.
Subject(s)
Columbidae , Food Preferences , Animals , Feathers , Pakistan , Plant BreedingSubject(s)
Coronavirus Infections , Neoplasms , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , Child , Humans , India/epidemiology , Neoplasms/epidemiology , Neoplasms/therapy , Pneumonia, Viral/epidemiology , SARS-CoV-2ABSTRACT
Juvenile myelomonocytic leukemia(JMML) is a pediatric myeloproliferative disorder. Allogeneic hematopoietic stem cell transplant (HSCT) is the only curative treatment for JMML. Pre-transplant therapy is a matter of controversy, and there are no firm recommendations. Whether chemotherapy is effective in achieving durable remission is questionable. Patients diagnosed as JMML at our center from January-2014 to December-2019 were retrospectively analyzed. All patients treated with at least one cycle of sequential therapy with subcutaneous cytarabine and oral 6-mercaptopurine were further assessed. The total number of patients diagnosed during the study period was 33. Patients were divided into two groups: patients who did not get any chemotherapy (n = 13) and ones who received at least one cycle of chemotherapy(n = 20). Age, total leukocyte count (TLC), monocyte percent, platelet count and spleen size were comparable between the two groups. There was no difference in the overall survival between the two groups, but 6 out of 20 patients showed a response to chemotherapy (2 complete remission, 4 partial remission). Two patients out of 20 underwent hematopoietic stem cell transplant (HSCT). The patients who achieved complete remission received 12 cycles of chemotherapy and have been in follow up for 28 months and 50 months respectively. Our results showed that sequential therapy with 6-mercaptopurine and cytarabine may be offered to patients in whom HSCT is not feasible or as a bridge therapy in those awaiting HSCT. The advantages of this approach include low cost, out-patient management and decreased requirement of blood components. In a subset of patients it may achieve remission.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cytarabine/administration & dosage , Leukemia, Myelomonocytic, Juvenile/drug therapy , Mercaptopurine/administration & dosage , Child, Preschool , Hematopoietic Stem Cell Transplantation/methods , Humans , Infant , Leukocyte Count , Platelet Count , Remission Induction , Retrospective Studies , Spleen , Treatment OutcomeABSTRACT
AIMS: The aim of this study was the molecular identification of Salmonella enterica serovar Infantis (S. Infantis) isolated from poultry samples and their antimicrobial resistance and virulence profiling. METHODS AND RESULTS: A total of 149 isolates, belonging to genus Salmonella, originally isolated from 340 suspected poultry post mortem specimens reported by us earlier were preliminary identified as Salmonella by biochemical methods and confirmed by polymerase chain reaction targeting genus-specific gene invA. Targeting serovar-specific gene fragment (fljB) resulted in confirmation of 54 isolates as S. Infantis which were further confirmed by sequencing of 16S RNA and fljB genes. Swimming and swarming motilities were detected in 98·1 and 11·1% isolates respectively. Phenotypic disc diffusion assay against 23 antimicrobial agents showed the highest resistance against pefloxacin (PEF) (94·4%), chloramphenicol (83·3%) and imipenem (77·7%) while 5·3% isolates showed extended-spectrum ß-lactamase production. Fifty-nine genes reported for antimicrobial resistance and 12 for conferring virulence were targeted. The most prevalent resistance gene for aminoglycosides was aadA (42·3%), for quinolone resistance determining region parE (62·5%), for penicillin's Int1 (62·9%), for chloramphenicol cat3 (66·1%) and for beta-lactams blaTEM -1 (44·4%). Among efflux pump coding genes, armA showed highest (74·2%) prevalence and for virulence, a high prevalence of SopE (89·2%) showed the zoonotic potential of the isolates. The activity of efflux pumps was detected through Ethidium Bromide-agar method. CONCLUSIONS: Poultry could act as reservoirs of multidrug resistance Salmonella. SIGNIFICANCE AND IMPACT OF THE STUDY: We firstly report the prevalence and molecular characterization of virulence/drug resistance in S. Infantis from this region and the results may contribute to designing precisely targeted therapy. This study has also highlighted the possible emergence of S. Infantis with zoonotic potential.
Subject(s)
Drug Resistance, Multiple, Bacterial , Poultry/microbiology , Salmonella enterica/physiology , Salmonella enterica/pathogenicity , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Drug Resistance, Multiple, Bacterial/genetics , Farms , Microbial Sensitivity Tests , Pakistan , Salmonella enterica/drug effects , Salmonella enterica/genetics , Serogroup , Virulence/geneticsABSTRACT
A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time or wounds that do not heal within three months are often considered chronic. Chronic wounds often remain in the inflammatory stage for too long and may never heal or may take years. Chronic wound patients often report pain as dominant in their lives. Persistent pain is the main problem for patients with chronic ulcers. Many wounds pose no challenge to the body's innate ability to heal; some wounds, however, may not heal easily either because of the severity of the wounds themselves or because of the poor state of health of the individual. Any wound that does not heal within a few weeks should be examined by a healthcare professional because it might be infected, might reflect an underlying disease.
ABSTRACT
Diagnostic kidney biopsies sometimes yield clinically unsuspected diagnoses. We present a case of a 69-year-old woman with established ANCA-associated vasculitis (AAV) of 4 years duration who was in clinical remission following cytotoxic therapy and was on maintenance immunosuppression. She presented to the hospital with acute kidney injury (AKI), symptoms suggestive of a systemic vasculitis, and in addition had hypercalcemia, metabolic alkalosis. A relapse in the AAV was suspected but a diagnostic kidney biopsy showed acute tubular necrosis, patchy interstitial inflammation, and calcium phosphate deposits. It was found that the patient recently started consuming large doses of over-the-counter calcium-containing antacids and vitamin Dcontaining multivitamin supplements. Cessation of these drugs led to improvement of renal function to baseline. This case highlights several teaching points: (1) the kidney biopsy can prove to be critically important even in cases where there appears to be a more obvious clinical diagnosis, (2) AK due to calcium-alkali syndrome has characteristic histopathological changes, and (3) that the triad of hypercalcemia, metabolic alkalosis, and AKI is exclusively associated with the ingestion of excessive quantities of calcium-containing antacids. The physician should keep this in mind, and pro-actively seek pertinent medication history from the patient. A brief review of calcium-alkali syndrome is given.
Subject(s)
Acute Kidney Injury/etiology , Antacids/adverse effects , Calcium/adverse effects , Dietary Supplements/adverse effects , Vitamin D/adverse effects , Aged , Alkalosis/chemically induced , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Female , Humans , Hypercalcemia/chemically induced , Kidney Tubular Necrosis, Acute/pathologyABSTRACT
Laurin-Sandrow syndrome (LSS) is a rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. The genetic basis of LSS is currently unknown. LSS shows phenotypic overlap with Haas-type polysyndactyly (HTS) regarding the digital phenotype. Here we report on five unrelated families with overlapping microduplications encompassing the Sonic hedgehog (SHH) limb enhancer ZPA regulatory sequence (ZRS) on chromosome 7q36. Clinically, the patients show polysyndactyly phenotypes and various types of lower limb malformations ranging from syndactyly to mirror image polydactyly with duplications of the fibulae. We show that larger duplications of the ZRS region (>80 kb) are associated with HTS, whereas smaller duplications (<80 kb) result in the LSS phenotype. On the basis of our data, the latter can be clearly distinguished from HTS by the presence of mirror image polysyndactyly of the feet with duplication of the fibula. Our results expand the clinical phenotype of the ZRS-associated syndromes and suggest that smaller duplications (<80 kb) are associated with a more severe phenotype. In addition, we show that these small microduplications within the ZRS region are the underlying genetic cause of Laurin-Sandrow syndrome.
Subject(s)
Abnormalities, Multiple/genetics , Ectromelia/genetics , Fingers/abnormalities , Foot Deformities, Congenital/genetics , Hand Deformities, Congenital/genetics , Hedgehog Proteins/genetics , Nose/abnormalities , Polydactyly/genetics , Regulatory Sequences, Nucleic Acid/genetics , Syndactyly/genetics , Toes/abnormalities , Abnormalities, Multiple/pathology , Chromosomes, Human, Pair 7/genetics , Ectromelia/pathology , Female , Fingers/pathology , Foot Deformities, Congenital/pathology , Gene Duplication , Gene Expression Regulation , Hand Deformities, Congenital/pathology , Humans , Male , Nose/pathology , Pedigree , Polydactyly/pathology , Syndactyly/pathology , Toes/pathologyABSTRACT
BACKGROUND: Woolly hair (WH) belongs to a family of disorders characterized by hair shaft anomalies that clinically presents with tightly curled hair, which can be divided into syndromic and non-syndromic forms of WH. We have recently identified mutations in both LPAR6/P2RY5 and LIPH that are associated with autosomal recessive woolly hair (ARWH). OBJECTIVE: To study the underlying genetic causes of autosomal woolly hair in Pakistani population. METHODS: We studied 10 Pakistani families with ARWH for mutations in LPAR6/P2RY5 and LIPH and then performed haplotype analysis to confirm their segregation in the families. RESULTS: We identified five mutations in LPAR6/P2RY5, among which three were recurrent and two were novel in eight Pakistani families. We then showed that two of the mutations in LPAR6/P2RY5 are founder mutations in Pakistani families. Moreover, we identified two recurrent mutations in the LIPH gene in two Pakistani families. CONCLUSION: Our study extends the spectrum of mutations in LPAR6/P2RY5 gene and underscores those mutations in LPAR6/P2RY5 and LIPH result in similar phenotypes.
Subject(s)
Hair Diseases/genetics , Hypotrichosis/genetics , Lipase/genetics , Mutation , Receptors, Lysophosphatidic Acid/genetics , Receptors, Purinergic P2/genetics , Female , Haplotypes , Humans , Male , PedigreeABSTRACT
UNLABELLED: A 50-year-old lady on hydrochlorothiazide (HCTZ) presented to the hospital after 4 days of generalized muscle aches and dark urine. She admitted to consuming one and a half bags of black licorice bites containing 2% natural licorice during the past 3 weeks. Examination showed high blood pressure, while labs revealed elevated creatine kinase, hypokalemia, hypocalcemia and hypophosphatemia with low aldosterone and plasma renin levels and high intact PTH. The active component of licorice is glycyrrhizic acid, which inhibits an enzyme required to convert cortisol to a less active metabolite, cortisone. This causes excess cortisol, simulating syndrome of apparent mineralocorticoid excess (AME), thus resulting in hypertension, hypokalemia and metabolic alkalosis. In our patient, licorice induced hypokalemia resulted in rhabdomyolysis. The rhabdomyolysis along with the effect of licorice led to secondary hypocalcaemia, which in turn triggered secondary hyperparathyroidism. This might have had a phosphaturic effect that caused hypophosphatemia, further worsening rhabdomyolysis. CONCLUSION: This case illustrates the complex relationship of various electrolytes, which can lead to self perpetuation of the disease, hence demanding more vigilance.
Subject(s)
Candy/adverse effects , Glycyrrhiza/adverse effects , Hypokalemia/chemically induced , Rhabdomyolysis/chemically induced , Biomarkers/blood , Female , Humans , Hyperparathyroidism, Secondary/chemically induced , Hypocalcemia/chemically induced , Hypokalemia/blood , Hypokalemia/therapy , Hypophosphatemia/chemically induced , Middle Aged , Rhabdomyolysis/blood , Rhabdomyolysis/therapy , Treatment OutcomeABSTRACT
BACKGROUND: Hypotrichosis with juvenile macular dystrophy (HJMD; OMIM 601553) is a rare autosomal recessive disorder characterized by hypotrichosis with short scalp hair and progressive macular dystrophy leading to blindness between the second and the fourth decades of life. HJMD is caused by mutations in the P-cadherin gene (CDH3), a member of the family of classical cadherins. METHODS: We analyzed the DNA from members of 2 consanguineous Pakistani families with HJMD for mutations in the P-cadherin gene through direct sequencing. RESULTS: We identified 2 splice site mutations in the P-cadherin gene in these families. One was a novel mutation, Ivs12-2A-->G and the other a recurrent mutation, Ivs10-1G-->T. A screening assay for the novel mutation ruled out the possibility of a polymorphism. Using haplotype analysis, we determined that the mutation, Ivs10-1G-->T, is a founder mutation in the Pakistani population. CONCLUSION: We identified 2 splice site mutations in the CDH3 gene leading to HJMD, further enriching our understanding of HJMD versus ectodermal dysplasia, ectrodactyly and macular dystrophy syndrome.
Subject(s)
Cadherins/genetics , Hypotrichosis/genetics , Macular Degeneration/genetics , Point Mutation , RNA Splice Sites/genetics , Adult , Base Sequence , Child , Consanguinity , Haplotypes , Humans , Male , PedigreeABSTRACT
BACKGROUND: Papillon-Lefevre syndrome (PLS; OMlM 245000) is an autosomal recessive disease caused by mutations in cathepsin C (CTSC) gene and is characterized by palmoplantar keratoderma, psoriasiform lesion over the extensor surfaces and gingivitis followed by loss of teeth. CTSC gene is expressed in several tissues including the skin and cells of the immune system. In the skin, CTSC plays a role in differentiation and desquamation, whereas in the immune system, it activates serine proteases. OBJECTIVES: We analysed the molecular basis of PLS in a Pakistani family. METHODS: Genomic DNA was isolated from the sample according to standard techniques. All exons of the CTSC gene with adjacent sequences of exon-intron borders were amplified by PCR and directly sequenced. RESULTS: We identified a novel deletion mutation designated c.2ldelG (Leu7PhefsX57) in exon 1 of the CTSC gene, which probably results in the absence of CTSC protein. CONCLUSION: Our data further expand the spectrum of mutations in the CTSC gene underlying PLS.
Subject(s)
Cathepsin C/genetics , Papillon-Lefevre Disease/ethnology , Papillon-Lefevre Disease/genetics , Sequence Deletion/genetics , Adult , Exons/genetics , Humans , Introns/genetics , Male , PakistanABSTRACT
BACKGROUND: Keratins are heteropolymeric proteins that form the intermediate filament cytoskeleton in epithelial cells. The common basic structure of all keratins is organized in a central α-helical rod domain flanked by nonhelical, variable head and tail regions. Most mutations in keratins are found in the central α-helical rod domain. Keratin 9 (K9) is expressed only in the suprabasal layers of palmoplantar epidermis. Mutations in the keratin 9 gene (KRT9) have been shown to cause epidermolytic palmoplantar keratoderma (EPPK; OMIM 144200), an autosomal dominant genodermatosis characterized clinically by diffuse hyperkeratosis limited to the palms and soles, and histologically by epidermolysis in suprabasal layers of the epidermis. AIM: To elucidate the genetic basis of EPPK in five Pakistani families. METHODS: Using microsatellite markers localized to the areas around the type I keratin gene cluster on chromosome 17q21, genotyping of these families was performed, followed by sequencing of the KRT9 gene. RESULTS: The analysis resulted in the identification of two novel (p.M157K and p.Y454H) and two recurrent (p.M157T and p.R163Q) mutations in the KRT9 of all five families. All mutations occurred within the highly conserved helix initiation or termination motif of K9. CONCLUSIONS: The affected members of all five families possess mutations in the KRT9 gene that severely affect heterodimer formation with the type II keratin partner. The results of our study further underscore the crucial role of K9 protein in the palmoplantar epidermis.
