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1.
Frontiers of Medicine ; (4): 1236-1249, 2023.
Article in English | WPRIM | ID: wpr-1010816

ABSTRACT

Primary ciliary dyskinesia (PCD) is a highly heterogeneous recessive inherited disorder. FAP54, the homolog of CFAP54 in Chlamydomonas reinhardtii, was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella. A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes. Through whole-exome sequencing, compound heterozygous variants c.2649_2657delinC (p. E883Dfs*47) and c.7312_7313insCGCAGGCTGAATTCTTGG (p. T2438delinsTQAEFLA) in a new suspected PCD-relevant gene, CFAP54, were identified in an individual with PCD. Two missense variants, c.4112A>C (p. E1371A) and c.6559C>T (p. P2187S), in CFAP54 were detected in another unrelated patient. In this study, a minigene assay was conducted on the frameshift mutation showing a reduction in mRNA expression. In addition, a CFAP54 in-frame variant knock-in mouse model was established, which recapitulated the typical symptoms of PCD, including hydrocephalus, infertility, and mucus accumulation in nasal sinuses. Correspondingly, two missense variants were deleterious, with a dramatic reduction in mRNA abundance from bronchial tissue and sperm. The identification of PCD-causing variants of CFAP54 in two unrelated patients with PCD for the first time provides strong supportive evidence that CFAP54 is a new PCD-causing gene. This study further helps expand the disease-associated gene spectrum and improve genetic testing for PCD diagnosis in the future.


Subject(s)
Mice , Animals , Humans , Male , Kartagener Syndrome/metabolism , Cilia/metabolism , Semen , Genetic Testing , RNA, Messenger , Mutation
2.
JOURNAL OF RARE DISEASES ; (4): 38-44, 2022.
Article in English | WPRIM | ID: wpr-1004981

ABSTRACT

Lymphangioleiomyomatosis (LAM) is a rare, multisystemic, low-grade neoplasm character-ized by diffuse cystic lesions in the lung.In recent years, emerging imaging examination such as 68Ga-NEB PET-CT scan provides efficient and precise non-invasive diagnostic methods to detect lymphatic circulation abnormalities in LAM patients. The long-term efficacy and safety of sirolimus for LAM has accumulated further evidence, and genetic profiling studies have unveiled more information of genetic mechanisms. Prognosis of LAM has been much improved. We briefly reviewed the research advances of LAM in China and other countires.

3.
Frontiers of Medicine ; (4): 150-155, 2022.
Article in English | WPRIM | ID: wpr-929187

ABSTRACT

Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.


Subject(s)
Humans , China , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Mutation , Poly T , RNA, Messenger/genetics
4.
Frontiers of Medicine ; (4): 933-937, 2021.
Article in English | WPRIM | ID: wpr-922509

ABSTRACT

Neurofibromatosis (NF) is a genetic disease in which the lungs are rarely involved. However, in NF cases with lung involvement, chest computed tomography may show bilateral basal reticulations, apical bullae, and cysts without bronchiectasis. Herein, we report a patient diagnosed with NF on the basis of the results of genetic testing who presented with early-onset wet cough and bronchiectasis. Considering the differential diagnosis of bronchiectasis combined with his early-onset wet cough, sinusitis, and sperm quality decline, we considered the possibility of primary ciliary dyskinesia (PCD). Further electron microscopy analysis of cilia and identification of homozygous mutations in the RSPH4A gene confirmed the diagnosis of PCD. Therefore, for patients with NF, when an image change exists in the lungs that does not correspond to NF, the possibility of other diagnoses, including PCD, must be considered.


Subject(s)
Humans , Cilia , Kartagener Syndrome/genetics , Microscopy, Electron , Mutation , Neurofibromatosis 1/genetics
5.
Frontiers of Medicine ; (4): 259-266, 2019.
Article in English | WPRIM | ID: wpr-772706

ABSTRACT

Lymphangioleiomyomatosis (LAM) is a rare diffuse cystic lung disease. Knowledge on LAM-related pulmonary hypertension (PH) is limited. This study aimed to analyze the clinical characteristics of LAM with elevated pulmonary artery pressure (PAP) and evaluate the potential efficacy of sirolimus. The study involved 50 LAM patients who underwent echocardiography. According to the tricuspid regurgitation velocity (TRV), these patients were divided into the TRV ⩽ 2.8 m/s group and TRV > 2.8 m/s group. Both groups comprised 25 females with an average age of 38.6 ± 8.1 and 41.5 ± 8.9 years. In the TRV > 2.8 m/s group, the estimated systolic PAP (SPAP) was significantly elevated (52.08 ± 12.45 mmHg vs. 30.24 ± 5.25 mmHg, P < 0.01). Linear analysis showed that SPAP was correlated with forced expiratory volume in 1 s (FEV), diffusing capacity of the lungs for carbon monoxide, alveolar arterial oxygen gradient (PO), and 6 min walking distance (r =-0.392, -0.351, 0.450, and -0.591, respectively; P < 0.05), in which PO was a risk factor for SPAP elevation (β = 0.064, OR = 1.066, P < 0.05). Moreover, in 10 patients who received sirolimus therapy, SPAP decreased from 57.0 12.6 mmHg to 35.2 ± 11.1 mmHg. The study showed that LAM patients with PH exhibit poor pulmonary function and hypoxemia and may benefit from sirolimus treatment.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Carbon Monoxide , Echocardiography , Exercise Test , Hemodynamics , Hypertension, Pulmonary , Therapeutics , Logistic Models , Lymphangioleiomyomatosis , Therapeutics , Multivariate Analysis , Oxygen , Blood , Therapeutic Uses , Respiratory Function Tests , Sirolimus , Therapeutic Uses
6.
Chinese Journal of Postgraduates of Medicine ; (36): 24-26, 2009.
Article in Chinese | WPRIM | ID: wpr-395284

ABSTRACT

Objective To describe and analyze the misdiagnosis and mistreatment status of pulmonary alveolar proteinosis (PAP), especially cases with combination of severe infection. Method The misdiagnosis and mistreatment of 84 PAP patients and 6 cases with combination of severe infection before admitting to PUMCH was analyzed retrospectively. Results 66.7%(56/84) had experienced misdiagnosis before admission. 32.1% (27/84) were misdiagnosed with idiopathic interstitial pneumonia (IIP) and 14.3% (12/84) with pulmonary tuberculosis. 88.1%(74/84) had received anti-infection treatment, 33.3%(28/84) received eortieosteroids, and 19.0%(16/84) received anti-tuberculosis treatment. The percentage of the pa-tients who had taken the bronchoscopic examination outside the PUMCH was 53.6%(45/84). The PAP pa-tients diagnosis was established through bronchoscopic examination (including BAL and TBLB) in 86.9% (73/84) patients. There were 6 patients who had severe infection when PAP established. All of these 6 cases had been misdiagnosed with IIP and received corticosteroids treatment, 2 of whom died. Conclusions The misdiagnosis and mistreatment happens commonly in PAP patients. The misuse of corticosteroids makes some PAP cases get the severe infection. The image feature and the examination of bronchoscopy, BAL and TBLB are the key point in avoiding misdiagnosis. The administration of corticosteroids in uncertain patients should be avoided.

7.
Chinese Journal of Geriatrics ; (12)2001.
Article in Chinese | WPRIM | ID: wpr-539537

ABSTRACT

Objective To study the difference of clinical manifestations,treatment and prognosis between idiopathic pulmonary fibrosis (IPF) and interstitial lung disease associated with connective tissue disorder, secondary pulmonary fibrosis(SPF). Methods The elderly patients≥ 60 yrs old, diagnosed as IPF or SPF in PUMC Hospital between 1990 and 2002 were reviewed and analyzed. Results Cough and dyspnea appeared to be the most common complaints in both groups. The most common signs were Velcro rales and clubbing fingers. The symptoms and signs were more common in IPF group. The mean course was shorter in SPF group (8.5 months vs 24.0 months). Mortality rate was high in both groups (26.3% and 30.0%) and showed no significant difference. The common causes of SPF were Sjogren syndrome, polymyositis, rheumatoid arthritis and progressive systemic sclerosis (9/40, 8/40, 7/40, 7/40, respectively). The most common radiograghic findings were bibasilar reticular patterns and showed more severe in IPF than in SPE〔41(71.9%) vs 14(35.0%)〕,P

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