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1.
Neumol. pediátr. (En línea) ; 14(2): 76-80, jul. 2019. ilus
Artigo em Espanhol | LILACS | ID: biblio-1014992

RESUMO

Primary ciliary dyskinesia is a congenital disorder due to abnormal motile ciliary function, especially in the airway epithelium. The mucociliary clearance is impaired, producing reoccurring respiratory tract infections, usually resulting in bronchiectasis as an adult. Patients also have frequent ear and sinus infections and almost 50% of them have situs inversus. Diagnosis of primary ciliary dyskinesia is difficult because there is not a single gold standard test, resulting in the need of a multi-test approach. Until recently in our country we only had transmission electron microscopy, but nasal nitric oxide and high speed video microscopy are now available. In this article we will detail the most important clinical characteristics that make us suspect the presence of primary ciliary dyskinesia at different ages and the methods available for its diagnosis.


La discinesia ciliar primaria es una enfermedad congénita debida a una alteración del movimiento normal de los cilios, especialmente a nivel del epitelio respiratorio. Esto se traduce en una alteración del clearance mucociliar lo que predispone al paciente a tener infecciones respiratorias repetidas, terminando en la aparición de bronquiectasias en la edad adulta. También son frecuentes las infecciones repetidas de oídos y cavidades perinasales. La presencia de situs inverso puede verse en hasta en 50% de los pacientes con esta enfermedad. El diagnóstico de discinesia ciliar primaria es difícil ya que no existe un examen que sea considerado patrón de oro, por lo que se requiere la realización de distintos exámenes. En nuestro país hasta hace poco tiempo solo contábamos con la microscopía electrónica, pero recientemente se ha sumado la medición de óxido nítrico nasal y la videomicroscopía de alta velocidad. En el presente artículo se detallarán las características clínicas más importantes que hacen sospechar la presencia de DCP en las distintas edades y los métodos disponibles para su diagnóstico.


Assuntos
Humanos , Recém-Nascido , Pré-Escolar , Adulto , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/genética , Síndrome de Kartagener/terapia , Cílios/ultraestrutura , Biópsia , Algoritmos , Testes Genéticos , Microscopia de Vídeo , Microscopia Eletrônica de Transmissão , Óxido Nítrico/análise
2.
Neumol. pediátr. (En línea) ; 14(2): 81-85, jul. 2019.
Artigo em Espanhol | LILACS | ID: biblio-1014999

RESUMO

At present, there is no specific treatment for primary ciliary dyskinesia, nor controlled and randomized clinical trials to determine how the management and monitoring of these patients should be considered. The therapeutic options are extrapolated from other diseases, such as cystic fibrosis, or non-cystic fibrosis bronchiectasis. However, the implementation of specific groups of experts, both in the USA (PDC-foundation) and in Europe (BESTCILIA or BEAT-PD), are helping to increase knowledge of the disease, opening research channels and seeking new treatments. Until we have therapies capable of correcting the basic defect of the disease, the pillars of treatment are the daily cleansing of the airways and aggressive antibiotherapy against respiratory infections. Multidisciplinary care in specialized centers where pulmonary function is monitored and the infection is prevented and treated will improve, as in cystic fibrosis, the results of patients.


En la actualidad no existe un tratamiento específico para la discinesia ciliar primaria, ni se cuenta con ensayos clínicos controlados y randomizados que permitan determinar cómo debe plantearse el manejo y seguimiento de estos pacientes. Las opciones terapéuticas son extrapoladas de otras enfermedades, como la fibrosis quística, o las bronquiectasias no fibrosis quística. Sin embargo, la puesta en marcha de grupos específicos de expertos, tanto en USA (PDC-foundation) como en Europa (BESTCILIA o BEAT-PD), están permitiendo incrementar el conocimiento de la enfermedad, abriendo vías de investigación y buscando nuevos tratamientos. Hasta contar con terapias capaces de corregir el defecto básico de la enfermedad, los pilares del tratamiento son la limpieza diaria de las vías aéreas y la antibioterapia agresiva frente a las infecciones respiratorias. La atención multidisciplinar en centros especializados donde se monitorice la función pulmonar y se prevengan y traten las infecciones mejorará, como en la fibrosis quística, los resultados de los pacientes.


Assuntos
Humanos , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/fisiopatologia , Síndrome de Kartagener/genética , Síndrome de Kartagener/terapia , Infecções Respiratórias/tratamento farmacológico , Seguimentos , Pneumopatias/fisiopatologia , Pneumopatias/terapia , Pneumopatias Fúngicas
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(3): 225-228, 2019 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-30835351

RESUMO

OBJECTIVE: To explore the clinical and genetic features of a child with primary ciliary dyskinesia. METHODS: Genomic DNA of the child and her parents was extracted and subjected to targeted gene capture and next generation sequencing. Suspected mutation was verified by Sanger sequencing, with its nature and impact predicted by Bioinformatic analysis. RESULTS: Clinical manifestations of the child mainly included severe pneumonia, bronchiectasia, nasosinusitis and pneumothorax. DNA sequencing showed that she has carried compound heterozygous mutations of the CCNO gene, namely c.848T>C (p.L283P) and c.262_263 insGGCCCGGCCC (p.Q88Rfs*51), which were respectively inherited from her mother and father. CONCLUSION: The child was diagnosed with primary ciliary dyskinesia caused by the compound heterozygous mutations of the CCNO gene.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Síndrome de Kartagener , Sequência de Bases , Feminino , Humanos , Síndrome de Kartagener/genética , Masculino , Mutação , Análise de Sequência de DNA
4.
Paediatr Respir Rev ; 29: 19-22, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30792130

RESUMO

Primary ciliary dyskinesia (PCD), also known as immotile-cilia syndrome, is a rare genetic disease that is inherited in an autosomal recessive manner. Several studies have explored certain aspects of PCD in the Arab world, yet much is still lacking in terms of identifying the different characteristics of this disease. In this paper, we aim to briefly cover those studies published about PCD in Arab countries, as well as to provide recommendations and guidelines for future studies.


Assuntos
Transtornos da Motilidade Ciliar/etnologia , Mundo Árabe , Árabes/genética , Transtornos da Motilidade Ciliar/diagnóstico , Transtornos da Motilidade Ciliar/genética , Transtornos da Motilidade Ciliar/terapia , Consanguinidade , Humanos , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/etnologia , Síndrome de Kartagener/genética , Síndrome de Kartagener/terapia , Kuweit , Oriente Médio , Guias de Prática Clínica como Assunto , Catar , Pesquisa , Arábia Saudita , Emirados Árabes Unidos , Iêmen
5.
Biomed Res Int ; 2018: 1854269, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29511670

RESUMO

Primary ciliary dyskinesia (PCD) is a clinical rare peculiar disorder, mainly featured by respiratory infection, tympanitis, nasosinusitis, and male infertility. Previous study demonstrated it is an autosomal recessive disease and by 2017 almost 40 pathologic genes have been identified. Among them are the leucine-rich repeat- (LRR-) containing 6 (LRRC6) codes for a 463-amino-acid cytoplasmic protein, expressed distinctively in motile cilia cells, including the testis cells and the respiratory epithelial cells. In this study, we applied whole-exome sequencing combined with PCD-known genes filtering to explore the genetic lesion of a PCD patient. A novel compound heterozygous mutation in LRRC6 (c.183T>G/p.N61K; c.179-1G>A) was identified and coseparated in this family. The missense mutation (c.183T>G/p.N61K) may lead to a substitution of asparagine by lysine at position 61 in exon 3 of LRRC6. The splice site mutation (c.179-1G>A) may cause a premature stop codon in exon 4 and decrease the mRNA levels of LRRC6. Both mutations were not present in our 200 local controls, dbSNP, and 1000 genomes. Three bioinformatics programs also predicted that both mutations are deleterious. Our study not only further supported the importance of LRRC6 in PCD, but also expanded the spectrum of LRRC6 mutations and will contribute to the genetic diagnosis and counseling of PCD patients.


Assuntos
Cílios/genética , Síndrome de Kartagener/genética , Proteínas/genética , Sequenciamento Completo do Exoma , China , Cílios/patologia , Exoma/genética , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Síndrome de Kartagener/diagnóstico por imagem , Síndrome de Kartagener/patologia , Masculino , Mutação , Linhagem , Tomografia Computadorizada por Raios X
6.
Reprod Biol Endocrinol ; 16(1): 10, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29402277

RESUMO

Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive disease with abnormalities in the structure of cilia, causing impairment of muco-ciliary clearance with respiratory tract infections, heterotaxia and abnormal sperm motility with male infertility. Here, with a comprehensive literature review, we report a couple with an infertility history of 9 years and three unsuccessful IVF treatments, where male partner has Kartagener's Syndrome, a subtype of PCD, displaying recurrent respiratory infections, dextrocardia and total asthenozoospermia. His diagnosis was verified with transmission electron microscopy and genetic mutation screening, revealing total absence of dynein arms in sperm tails and homozygous mutation in the ZMYND10, heterozygous mutations in the ARMC4 and DNAH5 genes. Laser assisted viability assay (LAVA) was performed by shooting the sperm tails during sperm retrieval for microinjection, following detection of pentoxifylline resistant immotile sperm. Live births of healthy triplets, one boy and two monozygotic girls, was achieved after double blastocyst transfer.


Assuntos
Infertilidade Masculina/terapia , Síndrome de Kartagener/complicações , Lasers , Nascimento Vivo , Análise do Sêmen/métodos , Espermatozoides/fisiologia , Sobrevivência Celular , Feminino , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/genética , Síndrome de Kartagener/genética , Síndrome de Kartagener/patologia , Masculino , Pentoxifilina , Gravidez , Injeções de Esperma Intracitoplásmicas , Espermatozoides/ultraestrutura
7.
Zhonghua Er Ke Za Zhi ; 56(2): 134-137, 2018 Feb 02.
Artigo em Chinês | MEDLINE | ID: mdl-29429202

RESUMO

Objective: To analyze the clinical manifestations, cilia ultrastructure and gene variations of primary ciliary dyskinesia (PCD). Methods: Analysis of three cases diagnosed as PCD by transmission electron microscopy of the endobronchial biopsy material in Division of Pediatric Pulmonology of Shandong Provincial Hospital between 2013 and 2016. Target gene sequence capture and next generation sequencing were used to analyze the gene. Related literatures on gene variation of PCD in Chinese were reviewed from Online Mendelian Inheritance in Man, Human Gene Mutation Database, PubMed and CNKI up to July 2017 by using search terms of "PCD" , "gene" , "Chinese". Results: There were one male and two females aged from 10 to 11 years. The common symptoms included recurrent respiratory infection, sinusitis and bronchiectasis. Two of them had situs inversus. Case 1 had lack of outer and inner dynein arms with compound heterozygous mutation of LRRC6. Case 2 had outer and inner dynein arms defects with heterozygous mutations of DNAH5 and DNAH11. Case 3 had abnormality in microtubule and inner dynein arms with homozygous mutation of CCDC39. All the variations mentioned above have not been reported before. Twelve cases have been reported about gene variations in PCD in Chinese from eight reports. All these patients had recurrent respiratory infection starting soon after birth, rhinosinusitis, and bronchiectasis. Nine of them had dextrocardia. Four cases have taken an effective nasal (or bronchial) mucosal biopsy. 1 case had inner and outer dynein arms defects. One case had inner dynein arms and radial spokes defects. One case had microtubule and central pair defects. And 1 case had normal cilia ultrastructure. Eight kinds of gene variations were found. Three cases had gene variations of DNAH5. 2 cases had gene variations of DYX1C1. 2 cases had gene variations of CCNO. There was 1 case with gene variations of CCDC39, CCDC40, HYDIN, ARMC4 and DNAI1 separately. Conclusions: Recurrent respiratory infection starting soon after birth, rhinosinusitis, and bronchiectasis are the common symptoms of PCD. Eleven of fifteen Chinese PCD patients with positive gene mutations were Kartagener syndrome. Cilia ultrastructure showed defects of inner and outer dynein arms, radial spokes, microtubule and central pair. Ten kinds of gene variations were found: DNAH5, DYX1C1, CCNO, CCDC39, CCDC40, HYDIN, ARMC4, DNAI1, LRRC6、DNAH11.


Assuntos
Cílios/fisiologia , Variação Genética , Síndrome de Kartagener/genética , Síndrome de Kartagener/fisiopatologia , Criança , Feminino , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Masculino , Mutação
8.
Thorax ; 73(2): 157-166, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28790179

RESUMO

RATIONALE: Primary ciliary dyskinesia is a genetically heterogeneous inherited condition characterised by progressive lung disease arising from abnormal cilia function. Approximately half of patients have situs inversus. The estimated prevalence of primary ciliary dyskinesia in the UK South Asian population is 1:2265. Early, accurate diagnosis is key to implementing appropriate management but clinical diagnostic tests can be equivocal. OBJECTIVES: To determine the importance of genetic screening for primary ciliary dyskinesia in a UK South Asian population with a typical clinical phenotype, where standard testing is inconclusive. METHODS: Next-generation sequencing was used to screen 86 South Asian patients who had a clinical history consistent with primary ciliary dyskinesia. The effect of a CCDC103 p.His154Pro missense variant compared with other dynein arm-associated gene mutations on diagnostic/phenotypic variability was tested. CCDC103 p.His154Pro variant pathogenicity was assessed by oligomerisation assay. RESULTS: Sixteen of 86 (19%) patients carried a homozygous CCDC103 p.His154Pro mutation which was found to disrupt protein oligomerisation. Variable diagnostic test results were obtained including normal nasal nitric oxide levels, normal ciliary beat pattern and frequency and a spectrum of partial and normal dynein arm retention. Fifteen (94%) patients or their sibling(s) had situs inversus suggesting CCDC103 p.His154Pro patients without situs inversus are missed. CONCLUSIONS: The CCDC103 p.His154Pro mutation is more prevalent than previously thought in the South Asian community and causes primary ciliary dyskinesia that can be difficult to diagnose using pathology-based clinical tests. Genetic testing is critical when there is a strong clinical phenotype with inconclusive standard diagnostic tests.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Síndrome de Kartagener/etnologia , Síndrome de Kartagener/genética , Proteínas Associadas aos Microtúbulos/genética , Mutação/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Paquistão/etnologia , Reino Unido , Adulto Jovem
9.
Auris Nasus Larynx ; 45(3): 585-591, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28939216

RESUMO

OBJECTIVE: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The early diagnosis of PCD is important for the prevention of long-term sequelae; however, this is often challenging because of the phenotypic heterogeneity of PCD and difficulty in genetic analysis. The majority of PCD patients in Japan are not diagnosed properly. To diagnose PCD more accurately, we developed a targeted next-generation sequencing (NGS) panel. METHODS: We examined 46 patients (age range, 1-64 years; 23 male and 23 female) who were clinically suspected of PCD. First, mutation hotspots in DNAH5 and DNAI1 were sequenced by the Sanger method. Next, exome sequencing was performed in 32 known PCD genes using our novel NGS panel with the Ion Torrent PGM system. Variant annotation was generated by Ion Reporter Version 5.0 (Life Technologies). Mutations found in the panel were validated by Sanger sequencing. RESULTS: Disease-causing gene mutations were found in 10 patients from 7 families: DNAH5 in 4 families, and DNAI1, CCDC40, and RSPH4A in 1 family each. Heterozygous mutations were found in 1 patient. The majority of the mutations found in the present analysis were novel. CONCLUSION: Japanese PCD patients have novel mutations in cilia-related genes. This targeted NGS panel can identify disease-causing mutations in patients with PCD.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Dineínas do Axonema/genética , Síndrome de Kartagener/genética , Proteínas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Japão , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNA , Adulto Jovem
10.
Rev. esp. pediatr. (Ed. impr.) ; 73(6): 361-364, nov.-dic. 2017.
Artigo em Espanhol | IBECS | ID: ibc-171616

RESUMO

Introducción. La discinesia ciliar primaria (DCP) es un conjunto de enfermedades caracterizadas por una disfunción de las estructuras ciliadas del epitelio bronquial y gonadal. Puede deberse a que los cilios sean inmóviles, tengan un movimiento ineficaz o, menos frecuentemente, a la ausencia total de los mismos. Como consecuencia de esta disfunción se producen las manifestaciones clínicas: bronquiectasias, sinusitis crónica y, en ocasiones, esterilidad en los varones. Se trata de la segunda causa más frecuente de enfermedad congénita respiratoria, por detrás de la fibrosis quística, con una herencia autosómica recesiva. Actualmente se están intentando identificar y definir los genes y mutaciones causantes de la enfermedad. Paciente. Se presenta un caso de DCP asociada a situs inversus en el que el diagnóstico se estableció por estudio genético. Presentamos el caso por la singularidad de la sospecha diagnóstica desde el periodo neonatal, por haberse realizado el diagnóstico a los 2 años, 9 meses (antes que la edad media habitual) y por la escasa prevalencia de la variante encontrada en la población europea. Resultados. Se identifica en este caso, en homozigosis, una variante: c.461A>C (p.H154P) en el gen CCDC103 (NM-213607.2), rara, ya que se encuentra en un 0,1% de la población europea (AU)


Introduction. Primary ciliary dyskinesia (DCP) englobes a set of diseases in which the microscopic cells in the respiratory and gonadal system do not function normally. This dysfunction is produced by immotile cilia, abnormal movement or, less frequent, absence of cilia at all. This ciliary dysfunction produces the different clinic manifestations, such as: chronic sinusitis, bronchiectasis and sometimes infertility in men. It usually follows autosomal recessive genetic inheritance. The genes responsible of this disorder are actually being identified. Patient. We present a case of DCP asociated to situs inversus, in wich the diagnosis was established with genetic study. This is a singular case, because the diagnosis was done sooner than the medium age (2 years and 9 months old), it was also suspected in the neonatal period and the low prevalence of this variant. Results. Exome sequencing identified a homozygous missense variant in CCDC103 (C.461A>C, p.H154P). This is a rare variant which only occurs in approximately 0.1% of european population (AU)


Assuntos
Humanos , Masculino , Pré-Escolar , Síndrome de Kartagener/genética , Doenças Respiratórias/congênito , Mutação/genética , Situs Inversus/complicações , Testes Genéticos/métodos , Doenças Genéticas Inatas/genética
11.
Eur Respir Rev ; 26(145)2017 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-28877972

RESUMO

Primary ciliary dyskinesia (PCD) is a rare genetic disease that affects the motility of cilia, leading to impaired mucociliary clearance. It is estimated that the vast majority of patients with PCD have not been diagnosed as such, providing a major obstacle to delivering appropriate care. Challenges in diagnosing PCD include lack of disease-specific symptoms and absence of a single, "gold standard", diagnostic test. Management of patients is currently not based on high-level evidence because research findings are mostly derived from small observational studies with limited follow-up period. In this review, we provide a critical overview of the available literature on clinical care for PCD patients, including recent advances. We identify barriers to PCD research and make suggestions for overcoming challenges.


Assuntos
Procedimentos Clínicos , Síndrome de Kartagener/terapia , Depuração Mucociliar , Procedimentos Clínicos/normas , Predisposição Genética para Doença , Humanos , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/epidemiologia , Síndrome de Kartagener/genética , Depuração Mucociliar/genética , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Encaminhamento e Consulta , Fatores de Risco
12.
Ultrastruct Pathol ; 41(6): 373-385, 2017 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28915070

RESUMO

Primary ciliary dyskinesia (PCD) is a genetic disorder causing chronic oto-sino-pulmonary disease. No single diagnostic test will detect all PCD cases. Transmission electron microscopy (TEM) of respiratory cilia was previously considered the gold standard diagnostic test for PCD, but 30% of all PCD cases have either normal ciliary ultrastructure or subtle changes which are non-diagnostic. These cases are identified through alternate diagnostic tests, including nasal nitric oxide measurement, high-speed videomicroscopy analysis, immunofluorescent staining of axonemal proteins, and/or mutation analysis of various PCD causing genes. Autosomal recessive mutations in DNAH11 and HYDIN produce normal TEM ciliary ultrastructure, while mutations in genes encoding for radial spoke head proteins result in some cross-sections with non-diagnostic alterations in the central apparatus interspersed with normal ciliary cross-sections. Mutations in nexin link and dynein regulatory complex genes lead to a collection of different ciliary ultrastructures; mutations in CCDC65, CCDC164, and GAS8 produce normal ciliary ultrastructure, while mutations in CCDC39 and CCDC40 cause absent inner dynein arms and microtubule disorganization in some ciliary cross-sections. Mutations in CCNO and MCIDAS cause near complete absence of respiratory cilia due to defects in generation of multiple cellular basal bodies; however, the scant cilia generated may have normal ultrastructure. Lastly, a syndromic form of PCD with retinal degeneration results in normal ciliary ultrastructure through mutations in the RPGR gene. Clinicians must be aware of these genetic causes of PCD resulting in non-diagnostic TEM ciliary ultrastructure and refrain from using TEM of respiratory cilia as a test to rule out PCD.


Assuntos
Cílios/ultraestrutura , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/genética , Microscopia Eletrônica de Transmissão , Medicina Molecular , Humanos
13.
Paediatr Respir Rev ; 24: 19-20, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28687245

RESUMO

Primary ciliary dyskinesia is an inherited disease characterized by impaired ciliary function leading to diverse clinical manifestations, including chronic sinopulmonary disease, persistent middle ear effusions, laterality defects, and infertility. Our understanding of the complex genetics and functional phenotypes of primary ciliary dyskinesia has rapidly grown, and over 35 disease-associated genes have been identified, which segregate into genes that encode axonemal motor proteins, regulatory proteins within the cilium, and cytoplasmic proteins involved in ciliary assembly. These findings have yielded unexpected insights into the clinical heterogeneity of disease and are beginning to revolutionize diagnostic testing for primary ciliary dyskinesia.


Assuntos
Cílios/ultraestrutura , Testes Genéticos , Síndrome de Kartagener/diagnóstico , Cílios/genética , Genótipo , Humanos , Síndrome de Kartagener/genética , Síndrome de Kartagener/patologia , Microscopia Eletrônica de Transmissão , Mutação , Fenótipo
14.
Zhonghua Er Ke Za Zhi ; 55(4): 304-307, 2017 Apr 02.
Artigo em Chinês | MEDLINE | ID: mdl-28441829

RESUMO

Objective: To review children's primary ciliary dyskinesia (PCD) in the pathogenesis, clinical manifestation, diagnosis and treatment. Method: To summarize and analyze the clinical data of a patient who was admitted to the first affiliated hospital of Xiamen University with primary ciliary dyskinesia in April 2014 while referring to related literature. Result: An 11 years old boy, weighting about 22 kg, had a course of more than 10 years with repeated cough, stuffy and runny nose shortly after the birth. Examinations after admission to hospital showed that he presented with visible clubbing, bilateral paranasal sinus area tenderness, pharynx posterior wall with visible yellow pussy stuff drip and bilateral lung had scattered wet rales. Auxiliary examination revealed bilateral maxillary sinus, ethmoid sinus inflammation and bronchitis with left lower lung bronchiectasis. Fiberoptic bronchoscopy discovered congestion and a lot of sputum; ciliary biopsy pathology displayed that cilia were sparse and partial cilia 9+ 2 microtubules structural abnormalities. Full sequence of exon gene sequencing revealed two mutations located at chromosome 16 chr16: 71061369 (non-coding regions) and chr16: 70993591 (coding). Two novel mutations m. 3362A>G(E20) and c. 6101G>A(E39) in exon 16 of the HYDIN gene were identified. With the" ciliary motility disorder, gene" as keywords , the CNKI, Wanfang digital knowledge service platform and PubMed were searched for relevant articles from the establishment to July 2016. The studies retrieved included 9 cases and these cases were summarized. Comprehensive analysis showed that HYDIN gene mutations related PCD patients had the typical PCD performance such as repeatedly wet cough, sinusitis, bronchiectasis, and otitis media. The majority of patients have a history of acute respiratory distress syndrome in infancy and no visceral dislocation was not found. Most of the patients had no obvious structural abnormalities in cilia electron microscopic examination. Conclusion: The PCD patients with HYDIN genes mutations have clinical manifestations such as sinusitis, otitis media, bronchiectasis but without transposition of viscera. Cilia structure can be normal under the electron microscopic examination in some of patients.


Assuntos
Síndrome de Kartagener/genética , Proteínas dos Microfilamentos/genética , Biópsia , Broncoscopia , Criança , Cromossomos Humanos Par 16 , Cílios , Éxons , Humanos , Masculino , Microscopia Eletrônica , Mutação
15.
Nat Commun ; 8: 14279, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28176794

RESUMO

By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2-DNAAF4-HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Dineínas do Axonema/metabolismo , Genes Ligados ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Síndrome de Kartagener/genética , Adolescente , Adulto , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Axonema/patologia , Criança , Pré-Escolar , Cílios/patologia , Cílios/ultraestrutura , Citoplasma/patologia , Modelos Animais de Doenças , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Células HEK293 , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Recém-Nascido , Síndrome de Kartagener/patologia , Masculino , Microscopia Eletrônica de Transmissão , Linhagem , Filogenia , Mutação Puntual , Dobramento de Proteína , Alinhamento de Sequência , Deleção de Sequência , Motilidade Espermática/genética , Sequenciamento Completo do Exoma , Peixe-Zebra
16.
Eur Respir Rev ; 26(143)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28096286

RESUMO

Primary ciliary dyskinesia is a genetic disease of ciliary function leading to chronic upper and lower respiratory tract symptoms. The diagnosis is frequently overlooked because the symptoms are nonspecific and the knowledge about the disease in the primary care setting is poor. Additionally, none of the available tests is accurate enough to be used in isolation. These tests are expensive, and need sophisticated equipment and expertise to analyse and interpret results; diagnosis is therefore only available at highly specialised centres. The diagnosis is particularly challenging in countries with limited resources due to the lack of such costly equipment and expertise.In this review, we discuss the importance of early and accurate diagnosis especially for countries where the disease is clinically prevalent but diagnostic tests are lacking. We review the diagnostic tests available in specialised centres (nasal nitric oxide, high-speed video microscopy, transmission electron microscopy, immunofluorescence and genetics). We then consider modifications that might be considered in less well-resourced countries whilst maintaining acceptable accuracy.


Assuntos
Países em Desenvolvimento/economia , Técnicas de Diagnóstico do Sistema Respiratório/economia , Custos de Cuidados de Saúde , Acesso aos Serviços de Saúde/economia , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/economia , Programas Nacionais de Saúde/economia , Análise Custo-Benefício , Diagnóstico Precoce , Humanos , Síndrome de Kartagener/genética , Síndrome de Kartagener/terapia , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes
17.
Eur Respir J ; 49(1)2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27836958

RESUMO

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.


Assuntos
Cílios/ultraestrutura , Síndrome de Kartagener/diagnóstico , Cílios/patologia , Técnica Delfos , Diagnóstico Diferencial , Europa (Continente) , Imunofluorescência , Testes Genéticos , Humanos , Síndrome de Kartagener/genética , Microscopia Eletrônica de Transmissão , Microscopia de Vídeo , Óxido Nítrico/análise , Literatura de Revisão como Assunto , Sociedades Médicas
18.
Asian J Androl ; 19(5): 515-520, 2017 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27270341

RESUMO

Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder resulting from the loss of normal ciliary function. Symptoms include neonatal respiratory distress, chronic sinusitis, bronchiectasis, situs inversus, and infertility. However, only 15 PCD-associated genes have been identified to cause male infertility to date. Owing to the genetic heterogeneity of PCD, comprehensive molecular genetic testing is not considered the standard of care. Here, we provide an update of the progress on the identification of genetic factors related to PCD associated with male infertility, summarizing the underlying molecular mechanisms, and discuss the clinical implications of these findings. Further research in this field will impact the diagnostic strategy for male infertility, enabling clinicians to provide patients with informed genetic counseling, and help to adopt the best course of treatment for developing directly targeted personalized medicine.


Assuntos
Infertilidade Masculina/genética , Síndrome de Kartagener/genética , Feminino , Heterogeneidade Genética , Humanos , Masculino
19.
J Assist Reprod Genet ; 34(2): 275-281, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27988889

RESUMO

PURPOSE: Kartagener syndrome (KS), also known as visceral inversion-nasosinusitis-bronchiectasis syndrome, or familial bronchiectasis, is an autosomal recessive inherited disease. In this study, through two cases of KS, we aimed to assess the clinical and genetic characteristics of KS caused by DNAH5 mutations. METHODS: The two cases of KS from the same family underwent extensive clinical assessments, with next-generation DNA sequencing and bioinformatics analysis to identify pathogenic genes. In addition, Sanger sequencing was used to verify the pedigrees. RESULTS: The present study employed a directional capture strategy for hereditary disease screening, which correctly identified the virulence sites in the pedigree, and facilitated the differential diagnosis among multiple genes. Two novel mutations were detected in DNAH5: c.7778C>T (missense mutation) and c.13729G>A (nonsense mutation). They were not found in dbSNP, 1000 Genomes, and ExAC. CONCLUSIONS: These findings demonstrated that new DNAH5 mutations could be used for molecular diagnosis of KS, providing families with genetic counseling and prenatal diagnosis.


Assuntos
Dineínas do Axonema/genética , Bronquiectasia/genética , Síndrome de Kartagener/genética , Bronquiectasia/diagnóstico , Bronquiectasia/patologia , Criança , Códon sem Sentido/genética , Códon sem Sentido/isolamento & purificação , Feminino , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/patologia , Masculino , Mutação de Sentido Incorreto/genética , Linhagem , Fenótipo
20.
Mol Med Rep ; 14(6): 5077-5083, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27779714

RESUMO

Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by structural and/or functional impairment of cilia throughout the whole body. Early diagnosis of PCD is important for the prevention of long­term sequelae, however early diagnosis is a challenge due to the phenotypic heterogeneity of PCD. In the current study, the patient with PCD was diagnosed at nine years old following several efforts to control intractable airway symptoms. The patient experienced a chronic productive cough beginning in early childhood and had multiple episodes of pneumonia and otitis media with effusion and sinusitis. No situs inversus or other heterotaxias were reported. Serial chest X­rays exhibited persistent atelectasis and bronchiectasis in the right middle lobe. When the patient was nine years old, electron microscopy of his cilia and genetic analysis were conducted. Electron microscopy of a biopsy specimen from the nasal mucosa indicated loss of the outer dynein arms. Whole­exome analysis of the genome demonstrated the presence of compound heterozygous mutations in DNAH5: NM_001369.2:c.5983C>T, p.Arg1995X in exon 36 and NM_001369.2:c.9101delG, p.Gly3034ValfsX22 in exon 54; neither of which have been previously reported in the literature in a Japanese patient. Notably, this case is, to the best of our knowledge, the first reported case of PCD caused by the DNAH5 mutation in a Japanese patient.


Assuntos
Dineínas do Axonema/genética , Síndrome de Kartagener/genética , Mutação , Criança , Análise Mutacional de DNA , Exoma , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Síndrome de Kartagener/diagnóstico , Masculino , Linhagem , Radiografia Torácica , Tomografia Computadorizada por Raios X
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