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Introduction: Hyperpigmentation is one of the most common reac?on to inflammatory, benign and malignant lesions of the skin. These disorders comprise heterogeneous group of diseases of epidermal and dermal hyperpigmenta?on divided into various types according to e?ology and pathology. Correct diagnosis of these hyperpigmented lesions is linked to histopathologic examina?on of skin biopsies with clinical correla?on. Aim: To study the spectrum of hyperpigmented skin lesions with reference to age and sex distribu?on. Materials and Methods: This prospec?ve cohort study was conducted at Department of Pathology, at Alluri Sitaramaraju Academy of Medical Sciences, Eluru, Andhra Pradesh, India, which included 80 pa?ents who were clinically diagnosed with hyperpigmented skin lesions in all age groups from July 2014 to August 2016. Frequency and percentage sta?s?cs was used to present the results. Results: Out of 80 cases, 34 cases of inflammatory lesions, 23 cases of benign lesions and 23 cases of malignant lesions were reported. Among the post inflammatory lesions the majority were classical Lichen planus. Conclusion: Most common lesion was lichen planus and its variants with highest incidence in females and age group greater than 60 years. Histopathological diagnosis with clinical correla?on aids in effec?ve management of the pa?ents.
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Duchenne/Becker muscular dystrophy(DMD/BMD)is a progressive, destructive neuromuscular disease.It is caused by mutations in the gene encoding dystrophy.The mutations come in various forms and the severity of the disease varies.The onset of the disease is insidious, and the initial manifestation is only abnormal serum enzymes.With the progression of the disease, the skeletal muscle and myocardial striated muscle cells are further destroyed, gait abnormalities and myocardial damage gradually appear, and eventually most children die of heart failure.At present, there is no effective radical cure.The existing treatment methods, including oral glucocorticoids and restoring functional dystrophin, are mostly limited to alleviate skeletal muscle symptoms, and are very limited to improve cardiac symptoms.This article reviews the progress in the diagnosis and treatment of myocardial damage in DMD/BMD, in order to provide reference for clinical research and gene therapy.
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Objective: To investigate the value of conventional MRI in differential diagnosis of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Methods: The imaging data of the hip and thigh muscles of 697 patients with dystrophinopathy were retrospectively analyzed, and the similarities and differences of signs between DMD and BMD were compared. Results: The distribution of muscle fat infiltration in DMD and BMD patients was consistent, the total fat infiltration degree of DMD patients was higher than BMD patients (P=0.034), with the most obvious gluteus maximus, rectus femoris and sartorius; there was no significant difference in the degree of total muscle edema (P=0.065), however, the edema of the posterior thigh and sartorius of DMD was significantly higher than that of BMD. The selective involvement of muscle atrophy and hypertrophy was consistent between DMD and BMD patients, the frequency of atrophy of BMD lateral femoris, middle femoris, medial femoris, Semimembranosus and long head of biceps was significantly higher than that of DMD (P0.05). Conclusion: Conventional MRI can differentiate DMD from BMD.
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Dystrophinopathy is a group of inherited diseases caused by the defect of dystrophin protein with X-linked recessive inheritance.The disease is clinically characterized by progressive severe muscles weakness and atrophy of proximal limb muscles and belt muscle,gastrocnemius pseudohypertrophy.The patient lose the ability of daily exercise,and ultimately succumb to restrictive lung disease or cardiac death.According to the clinical manifestations and the defect degree of dystrophin protein,dystrophinopathy is divided into:Duchenne muscular dystrophy (DMD),Becker muscular dystrophy,X-linked dilated cardiomyopathy,and female carrier of DMD.Patients can present with multi-system involvement at different stages of the disease,which require multidisciplinary management to alleviate symptoms,prolong life and improve quality of life.Glucocorticoids can significantly extend the independent activity of children by 2-5 years.Due to the high incidence,poor quality of life in the early stage and high disability and lethality in the late stage,it is important to strengthen the understanding of neurologists about this disease and conduct early diagnosis,full management and genetic counseling.
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Introducción: Las distrofias musculares son las enfermedades degenerativas más comunes dentro de las enfermedades neuromusculares, cursan con debilidad muscular que progresa hasta la pérdida de la deambulación y en la segunda década de vida surgen complicaciones cardíacas, respiratorias y ortopédicas. Objetivo: Analizar el estado actual de los tratamientos génico y farmacológico en las distrofias musculares de Duchenne y Becker Métodos: Se realizó una búsqueda en los meses de enero, febrero y marzo de 2018 en las bases de datos Medline, Cinhal, Web Of Science y Scopus. Se obtuvieron 232 resultados y después de aplicar los criterios de inclusión y exclusión, se consiguieron para analizar 15 artículos válidos para la revisión. Resultados: Los artículos analizados investigan mayoritariamente el efecto de las terapias mencionadas a nivel de funcionalidad y de síntesis de la proteína distrofina durante períodos largos, en los que participan muestras de tamaño y edades variadas tanto como distrofia muscular de Duchenne y como distrofia muscular de Becker. Conclusiones: Existen más artículos enfocados en la distrofia muscular de Duchenne que en la distrofia muscular de Becker. Esto puede ser debido a que la primera es la más grave y de peor pronóstico. Sigue siendo necesario realizar más estudios para avanzar sobre el estado actual de estos tratamientos(AU)
Introduction: Muscular dystrophies are one of the most common degenerative pathologies within neuromuscular diseases. They present muscular weakness that develops until loss of wandering and in the second decade of life can appear cardiac, respiratory and orthopaedic complications. Objective: To know the current state of genetic and pharmacology treatments in the Duchenne and Becker muscular dystrophies. Methods: A search was made from January to March 2018 at Medline, Cinhal, Web Of Science and Scopus databases. 232 results were obtained, and applying the inclusion and exclusion criteria, 15 acceptable articles for reviewing were found. Results: Analyzed articles mostly investigate the effect of the mentioned therapies in the levels of functionality and dystrophin protein synthesis during long periods, in which samples of different sizes and ages are used. Conclusions: There are more articles focused on Duchenne Muscular Dystrophy than Becker Muscular Dystrophy. That can be due to the fact that the first is the most severe and with the worst prognosis. It is still necessary to carry out more scientific studies to move forward from the current stage of these treatments(AU)
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Humanos , Distrofia Muscular de Duchenne/tratamiento farmacológico , Orden Génico/genética , Proteínas Relacionadas con la Folistatina/uso terapéutico , Edición Génica/métodosRESUMEN
Background: The cause of muscular dystrophies is genetic. It is a disorder of muscular system. The classification of the muscular dystrophies is based on the signs and symptoms. Present study was done to evaluate the profile, types, duration and severity of muscular dystrophy at a tertiary care hospital.Methods: A hospital based cross sectional study was carried out at department of General Medicine, Malla Reddy Institute of Medical Sciences, Hyderabad from October 2015 to December 2017. During the study period, it was possible to study the 20 cases of muscular dystrophy.Results: Muscular dystrophy was more common in males. Maximum cases were of Duchenne type of muscular dystrophy. Majority of the patients presented at 5-10 years of age. Muscular dystrophy was seen in early childhood. Out of 10 patients of Duchenne muscular dystrophy five patients were of grade I. There was no correlation between the duration of the disease and the severity of the disability. All patients had lower limb proximal weakness. Pathological Q wave (width > 30 ms) and Pathological Q wave (depth >more than 25% of the QRS amplitude) were present in 35% of the cases. All patients had rhythm NSR and QRS +60 to +75. Conduction abnormality was present in 5% of the cases. In half of the patients, serum creatinine kinase levels are moderately elevated.Conclusions: Muscular dystrophies are a common disorder of the childhood. Detailed studies will help to focus more light on this condition to improve outcome in future patients.
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Objective: To deepen the understanding of Duchenne/Becker muscular dystrophy by investigating dystrophin (DMD) gene variants in 2 Chinese Han families with this disease. Methods: Retrospective analysis of the clinical characteristics of the probands in two families with Duchnne/ Becker muscular dystrophy and the results of multiplex ligation-dependent probe amplification (MLPA) for the probands and their relatives was performed. Results: Three probands were identified by significantly-elevated creatine kinase levels. Two probands in family one are fraternal twin brothers with the same deletions of exons 8-9, while their mother has no abnormality at this site. The proband in family two is the little brother in a pair of fraternal twins with duplication of exons 48-51, and his mother has heterozygous duplication of exons 48-51. Conclusion: ① The presence of the same DMD gene mutation in the fraternal twins suggests that the mother may be a gonad chimera with this mutation if her gene detection of peripheral blood is normal. The mother must undergo prenatal gene diagnosis to reduce the risk of Duchenne/Becker muscular dystrophy in her offsprings. ② The exons 48-51 duplication of DMD gene is pathogenic mutation.
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<p><b>Background</b>Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are common X-linked recessive neuromuscular disorders caused by mutations in dystrophin gene. Multiplex polymerase chain reaction (multiplex PCR) and multiplex ligation-dependent probe amplification (MLPA) are the most common methods for detecting dystrophin gene mutations. This study aimed to contrast the two methods and discern the genetic characterization of patients with DMD/BMD in Eastern China.</p><p><b>Methods</b>We collected 121 probands, 64 mothers of probands, and 15 fetuses in our study. The dystrophin gene was detected by multiplex PCR primarily in 28 probands, and MLPA was used in multiplex PCR-negative cases subsequently. The dystrophin gene of the remaining 93 probands and 62 female potential carriers was tested by MLPA directly. In fetuses, multiplex PCR and MLPA were performed on 4 fetuses and 10 fetuses, respectively. In addition, sequencing was also performed in 4 probands with negative MLPA.</p><p><b>Results</b>We found that 61.98% of the subjects had genetic mutations including deletions (50.41%) and duplications (11.57%). There were 43.75% of mothers as carriers of the mutation. In 15 fetuses, 2 out of 7 male fetuses were found to be unhealthy and 2 out of 8 female fetuses were found to be carriers. Exons 3-26 and 45-52 have the maximum frequency in mutation regions. In the frequency of exons individually, exon 47 and exon 50 were the most common in deleted regions and exons 5, 6, and 7 were found most frequently in duplicated regions.</p><p><b>Conclusions</b>MLPA has better productivity and sensitivity than multiplex PCR. Prenatal diagnosis should be applied in DMD high-risk fetuses to reduce the disease incidence. Furthermore, it is the responsibility of physicians to inform female carriers the importance of prenatal diagnosis.</p>
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Femenino , Humanos , Masculino , Embarazo , China , Distrofina , Genética , Exones , Genética , Eliminación de Gen , Heterocigoto , Reacción en Cadena de la Polimerasa Multiplex , Distrofia Muscular de Duchenne , Genética , Mutación , Genética , Eliminación de SecuenciaRESUMEN
BACKGROUND AND PURPOSE: Studies of cases of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) confirmed by multiplex ligation-dependent probe amplification (MLPA) have determined the clinical characteristics, genotype, and relations between the reading frame and phenotype for different countries. This is the first such study from India. METHODS: A retrospective genotype-phenotype analysis of 317 MLPA-confirmed patients with DMD or BMD who visited the neuromuscular clinic of a quaternary referral center in southern India. RESULTS: The 317 patients comprised 279 cases of DMD (88%), 32 of BMD (10.1%), and 6 of intermediate phenotype (1.9%). Deletions accounted for 91.8% of cases, with duplications causing the remaining 8.2%. There were 254 cases of DMD (91%) with deletions and 25 (9%) due to duplications, and 31 cases (96.8%) of BMD with deletions and 1 (3.2%) due to duplication. All six cases of intermediate type were due to deletions. The most-common mutation was a single-exon deletion. Deletions of six or fewer exons constituted 68.8% of cases. The deletion of exon 50 was the most common. The reading-frame rule held in 90% of DMD and 94% of BMD cases. A tendency toward a lower IQ and earlier wheelchair dependence was observed with distal exon deletions, though a significant correlation was not found. CONCLUSIONS: The reading-frame rule held in 90% to 94% of children, which is consistent with reports from other parts of the world. However, testing by MLPA is a limitation, and advanced sequencing methods including analysis of the structure of mutant dystrophin is needed for more-accurate assessments of the genotype-phenotype correlation.
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Niño , Humanos , Estudios de Cohortes , Distrofina , Exones , Estudios de Asociación Genética , Genotipo , India , Reacción en Cadena de la Polimerasa Multiplex , Distrofia Muscular de Duchenne , Fenotipo , Sistemas de Lectura , Derivación y Consulta , Estudios Retrospectivos , Silla de RuedasRESUMEN
PURPOSE: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are similar genetic disorders whose patterns of mutation and disease phenotypes might be expected to show differences among different countries. We analyzed multiplex ligation-dependent probe amplification (MLPA) data in a large number of Korean patients with DMD/BMD. MATERIALS AND METHODS: We obtained 130 positive MLPA results (86 DMD, 27 BMD, and 17 female carriers) from 272 candidates (237 clinically suspected patients and 35 possible female carriers) who took part in this study. We analyzed the mutation patterns among 113 patients diagnosed by MLPA and calculated deletion/duplication percentages from a total of 128 patients, including 15 patients who were diagnosed using methods other than MLPA. We also analyzed hot spot locations among the 130 MLPA-positive results. RESULTS: Most mutations were detected in a central hot spot region between exons 44 and 55 (80 samples, 60.6%). Unlike previous reports, a second frequently observed hot spot near the 5'-end was not distinctive. MLPA detected deletions in specific exons in 92 patients with DMD/BMD (71.8%) and duplications in 21 patients (16.4%). CONCLUSION: Our MLPA study of a large number of Korean patients with DMD/BMD identified the most frequent mutation hot spot, as well as a unique hot spot pattern. DMD gene mutation patterns do not appear to show significant ethnic differences.
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Femenino , Humanos , Exones , Reacción en Cadena de la Polimerasa Multiplex , Distrofias Musculares , Distrofia Muscular de Duchenne , FenotipoRESUMEN
Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are X-linked neuromuscular disorders characterized by progressive muscle weakness and severe skeletal muscle degeneration. BMD is a milder form with a later onset. Patients with BMD tend to survive much longer than those with DMD. The differentiation between DMD and BMD is important in the genetic counseling of affected patients and their families. Since muscle biopsies are invasive procedures, the differential diagnosis of BMD and DMD is often dependent on the mutation identified in the DMD gene in affected patients. However, when a novel DMD mutation is identified, the differential diagnosis should be based on muscle biopsy findings with other clinical findings. Here we describe two Korean patients with BMD confirmed by muscle biopsy and genetic testing. Two novel exonic deletions in the DMD gene were identified.
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Humanos , Biopsia , Diagnóstico Diferencial , Exones , Asesoramiento Genético , Pruebas Genéticas , Debilidad Muscular , Músculo Esquelético , Distrofias Musculares , Distrofia Muscular de DuchenneRESUMEN
Objective To analyze the clinical characteristics of Duchenne/ Becker muscular dystrophy (DMD/BMD)with the initial presentation of transaminase elevation,in order to improve the clinician's understanding of this disease,and reduce misdiagnosis and missed diagnosis. To investigate the relationship between the elevation of transami-nase and the early stage of DMD/ BMD,and to provide the strategy for early diagnosis. Methods Twenty - four pa-tients admitted to the hospital with elevated serum transaminase as the initial presentation from January 2012 to Decem-ber 2014,who were diagnosed as DMD/ BMD by genetic testing or muscle biopsy,were enrolled. Their clinical data and laboratory examinations were retrospectively analyzed,including clinical features,diagnostic steps,serum muscle en-zymes,genetic analysis,electromyography and muscle pathological changes. Results The 24 patients were all male without family history of DMD/ BMD prior to birth. The average visiting age was (3. 4 ± 1. 2)years (ranging from 0. 8 to 6. 1 years),and 87. 5％ (21 / 24 cases)of cases were preschool children aged 2 - 6 years. Hypertransaminasemia was found in 21 cases (87. 5％)during the kindergarten physical examination,1 case during pre - operative investigation and 2 cases during respiratory infection. Due to its insidious onset,the time interval between incidental finding of elevated transaminase and definitive diagnosis was between 0. 6 and 20. 4 months. Among them,16 cases (66. 7％)had obvious pseudohypertrophy of calf muscles,and 18 cases (81. 8％)showed different degrees of movement disorder,such as unable to jump,easy to fall,and difficulty in climbing stairs. In addition,18. 2％ cases (4 / 22 cases)had a delay in language development. The serum alanine aminotransferase and aspartate aminotransferase levels were 120. 3 - 761. 7 U/ L and 83. 3 - 675. 5 U/ L,respectively. Serum creatine kinase (CK)was found to be markedly elevated (ranging from 3940 to 27510 U/ L)in all patients. Electromyography showed myogenic damage in 13 / 23 cases (56. 5％). DMD gene deletions were found in 18 cases (75. 0％),and duplications in 4 cases (16. 7％). The muscle biopsy performed in 2 cases (8. 3％)multiplex ligation - dependent probe amplification (MLPA)- negative cases showed evidence of dystrophic features on routine histology. Immunohistochemistry showed absent dystrophin staining in all 2 MLPA - nega-tive cases. Conclusion The clinical manifestation of DMD/ BMD is not typical in the early stage,so it is easy to be neglected or misdiagnosed. Elevated ALT and AST are important clues in the early diagnosis of DMD/ BMD. Children with elevated transaminase,in the absence of other signs and symptoms of hepatic injury,may have occult muscular di-sease,most frequently DMD/ BMD. A thorough physical examination and history taking as well as the measurement of serum CK are helpful in the differential diagnosis. Genetic testing or muscle biopsy should be done early for correct diagnosis of DMD/ BMD.
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El nevo de Becker, es un hamartoma cutáneo benigno de etiología desconocida, que se presenta como una mácula hiperpigmentada de bordes geográficos. Por lo general, se ubica en la región torácica superior y su compromiso tiende a ser unilateral. Ocasionalmente el nevo de Becker se asocia a anomalías en el tejido óseo, muscular o cutáneo, siendo la ictiosis una característica muy infrecuente. La presencia de alguna de estas anomalías asociadas a un Nevo de Becker determina el síndrome del Nevo de Becker. Paciente de sexo masculino de 18 años, que consultó por un cuadro iniciado en la infancia, caracterizado por la aparición de manchas cafés, escamosas, pruriginosas que inicialmente se ubicaron en las extremidades inferiores y con el tiempo fueron apareciendo en tronco, región lumbar y glútea. Mediante la correlación clínico-patológica se llegó al diagnóstico de Nevo de Becker, con características ictiosiformes. Se realizaron estudios complementarios con ecocardiograma Doppler y radiografía de tórax, que resultaron normales y una ecotomografía Doppler color de tórax anterior que mostró una leve ginecomastia bilateral con discreto aumento del botón mamario derecho y una leve hipoplasia del pectoral mayor derecho diagnosticándose Síndrome de Nevo de Becker. La mayoría de los reportes de Síndrome de nevo de Becker describen anomalías como escoliosis o hipoplasia unilateral de la mama, con escasos reportes sobre ictiosis. Se reporta este caso por su presentación atípica con múltiples nevos de Becker, compromiso de hemicuerpo inferior y su asociación ictiosiforme poco descrita en la literatura.
Becker's nevus is a benign cutaneous hamartoma of unknown etiology; it appears as a hyperpigmented macula with geographical borders. Usually it is located in the upper thoracic region, unilaterally. Occasionally Becker nevus is associated with abnormalities in the bony, muscle or skin tissue, being ichthyosis an unusual feature. The presence of some of these anomalies associated with Becker´s nevus determine the Becker´s nevus syndrome. Male patient of 18 years old who had a clinical history that begun in childhood, characterized by the appearance of brown, scaly, itchy patch that initially were located in the lower extremities and eventually were appearing in the trunk, lumbar and gluteal area. The clinical-pathological correlation led us to the diagnosis of Becker´s nevus with ichthyosiform features. Additional studies were performed such as Doppler echocardiography and chest radiograph, both normal. Color Doppler ultrasonography of anterior chest showed a slight bilateral gynecomastia with discrete increase of the right breast and a slight hypoplasia of the right major pectoral, determining a Becker´s nevus syndrome. Most reports of Becker´s nevus syndrome described abnormalities such as scoliosis or unilateral breast hypoplasia, few cases have been reported with ichthyosis. This case is reported for its atypical presentation with multiple Becker´s nevus, compromise of the lower body and its ichthyosiform association, rarely described in the literature.
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Humanos , Masculino , Adolescente , Hamartoma/diagnóstico , Nevo Pigmentado/diagnóstico , Síndrome , Biopsia , Hamartoma/complicaciones , Hamartoma/patología , Nevo Pigmentado/patologíaRESUMEN
BACKGROUND: Although Becker's nevus (BN) is a relatively common disease, the systematic studies of clinicopathological and immunohistochemical results are poorly reported. OBJECTIVE: To investigate the clinicopathological features and immunohistochemical alterations of keratinocyte proliferation, melanocyte density, smooth muscle hyperplasia and nerve fiber distribution in BN. METHODS: Clinical and pathological data were collected in 60 newly-diagnosed BN cases. Immunohistochemical stain of Ki-67, Melan-A, keratin 15, smooth muscle actin and protein gene product 9.5 was performed in 21 cases. RESULTS: The median diagnostic and onset age was 17 and 12 years, respectively. Skin lesions usually appeared on the upper trunk and upper limbs. The pathological features included the rete ridge elongation and fusion and basal hyperpigmentation. Epidermal Ki-67, Melan-A and keratin 15 expression and dermal nerve fiber length were significantly higher in lesional and perilesional skin than in normal skin (p<0.05~0.01), while smooth muscle actin expression was upregulated only in skin lesion (p<0.05). CONCLUSION: Although the clinical diagnosis of BN is often straightforward, histopathology is helpful to differentiate from other pigmentary disorders. The hyperproliferation of keratinocytes, melanocytes, arrector pili muscle and dermal nerve fibers could be involved in the pathogenesis of BN.
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Actinas , Edad de Inicio , Diagnóstico , Hiperpigmentación , Hiperplasia , Queratina-15 , Queratinocitos , Antígeno MART-1 , Melanocitos , Músculo Liso , Fibras Nerviosas , Nevo , Piel , Extremidad SuperiorRESUMEN
El nevus de Becker es un nevus organoide caracterizado por la aparición de uno o más parches hiperpigmentados, de bordes irregulares, que se localizan, con un patrón en damero, preponderantemente en la parte superior del tórax y la región escapular o proximal de las extremidades superiores (aunque pueden afectar cualquier parte del cuerpo). La asociación de este nevus con anomalías sistémicas, como hipoplasia mamaria unilateral y anomalías musculares, esqueléticas y/o cutáneas, se ha denominado síndrome del nevus de Becker. Presentamos 4 casos de niños con nevus de Becker y otras anomalías asociadas.
Becker´s nevus is an organoid nevus that manifests as one ore more hyperpigmented patches, with irregular margins, arranged in a checkerboard pattern, more often located in the upper half of the thorax, shoulder or proximal upper extremities, but it can be seen in any part of the body. The association of this nevus with unilateral breast hypoplasia, muscle, skeletal and/or skin anomalies has been named Becker´s nevus syndrome. We report 4 cases of children with Becker´s nevus syndrome and other associated anomalies.
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Humanos , Masculino , Adolescente , Femenino , Niño , Hamartoma/patología , Mama/anomalías , Neoplasias Cutáneas/patología , Nevo Pigmentado/patologíaRESUMEN
CONTEXT: Multiplex ligation probe amplification (MLPA) is a new technique to identify deletions and duplications and can evaluate all 79 exons in dystrophin gene in patients with Duchenne muscular dystrophy (DMD). Being semi-quantitative, MLPA is also effective in detecting duplications and carrier testing of females; both of which cannot be done using multiplex PCR. It has found applications in diagnostics of many genetic disorders. AIM: To study the utility of MLPA in diagnosis and carrier detection for DMD. MATERIALS AND METHODS: Mutation analysis and carrier detection was done by multiplex PCR and MLPA and the results were compared. RESULTS AND CONCLUSIONS: We present data showing utility of MLPA in identifying mutations in cases with DMD/BMD. In the present study using MLPA, we identified mutations in additional 5.6% cases of DMD in whom multiplex PCR was not able to detect intragenic deletions. In addition, MLPA also correctly confirmed carrier status of two obligate carriers and revealed carrier status in 6 of 8 mothers of sporadic cases.
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Distrofina , Femenino , Humanos , Masculino , Proteínas de la Membrana/análisis , Reacción en Cadena de la Polimerasa Multiplex/métodos , Distrofia Muscular de Duchenne/genética , Reacción en Cadena de la Polimerasa/métodosRESUMEN
Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessive disorders caused by mutation in dystrophin gene. We analyzed the results of a genetic test in 29 DMD/BMD patients, their six female relatives, and two myopathic female patients in Korea. As the methods developed, we applied different procedures for dystrophin gene analysis; initially, multiplex polymerase chain reaction was used, followed by multiplex ligation-dependent probe amplification (MLPA). Additionally, we used direct DNA sequencing for some patients who had negative results using the above methods. The overall mutation detection rate was 72.4% (21/29) in DMD/BMD patients, identifying deletions in 58.6% (17/29). Most of the deletions were confined to the central hot spot region between exons 44 and 55 (52.9%, 7/19). The percentage of deletions and duplications revealed by MLPA was 45.5% (5/11) and 27.2% (3/11), respectively. Using the MLPA method, we detected mutations confirming their carrier status in all female relatives and symptomatic female patients. In one patient in whom MLPA revealed a single exon deletion of the dystrophin gene, subsequent DNA sequencing analysis identified a novel nonsense mutation (c.4558G > T; Gln1520X). The MLPA assay is a useful quantitative method for detecting mutation in asymptomatic or symptomatic carriers as well as DMD/BMD patients.
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Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Análisis Mutacional de ADN , Distrofina/genética , Exones , Heterocigoto , Reacción en Cadena de la Ligasa , Reacción en Cadena de la Polimerasa Multiplex , Distrofia Muscular de Duchenne/genética , Mutagénesis Insercional , República de Corea , Análisis de Secuencia de ADN , Eliminación de SecuenciaRESUMEN
An 18-year-old boy was admitted with chest discomfort, nausea, and dyspnea at rest. At the age of 3 years, he underwent muscle biopsy and dystrophin gene analysis owing to an enlarged calf muscle and elevated serum kinase level (6,378 U/L) without overt weakness; based on the results, Becker muscular dystrophy (BMD) was diagnosed. The dystrophin gene showed deletion of exons 45 to 49. He remained ambulant and could step upstairs without significant difficulties. A chest roentgenogram showed cardiomegaly (cardiothoracic ratio, 54%), and his electrocardiogram (ECG) showed abnormal ST-T wave, biatrial enlargement, and left ventricular hypertrophy. The 2-dimensional and M-mode ECGs showed a severely dilated left ventricular cavity with diffuse hypokinesis. The systolic indices were reduced, including fractional shortening (9%) and ejection fraction (19%). Despite receiving intensive medical treatment, he died from congestive heart failure 5 months after the initial cardiac symptoms. We report a case of BMD with early-onset dilated cardiomyopathy associated with deletion of exons 45 to 49. Early cardiomyopathy can occur in BMD patients with certain genotypes; therefore, careful follow-up is required even in patients with mild phenotypes of BMD.