Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice / 医学前沿

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

A de novo GJA1 mutation identified by whole-exome sequencing in a patient with oculodentodigital dysplasia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic basis for a patient with oculodentodigital dysplasia.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole-exome sequencing was carried out for the trio family. Suspected mutation was verified by Sanger sequencing.</p><p><b>RESULTS</b>A de novo c.412G>A mutation of the GJA1 gene was identified in the patient, which was validated by Sanger sequencing.</p><p><b>CONCLUSION</b>The c.412G>A mutation of the GJA1 gene probably underlies the disease in the patient.</p>

The platelet characteristics of 22q11 microdeletion and its clinical application / 中国医师杂志

Objective 22q11 microdeletion is featured with hemotological dysfunction,among others:hypocalcemia,thrombocytopenia and megathrombocyte.This study was trying to work out the platelet characteristics of 22q1 1 microdeletion patients and its potential clinical application.Methods A total of 80 cases who had undergone open-heart surgery were selected and confirmed with fluorescence in situ hybridization (FISH) to have 22q1 1 microdeletion among 40 cases while the others were negative.The relevant data in full blood routine of all the 80 cases in hospital information system (HIS) then were collected and analyzed with suitable statistical methods.Results The mean platelet volume in microdeletion group was statistically higher than that in the control group [(11.20 ± 1.94)fL vs (8.95 ± 1.58) fL,P ＜0.01].The area under the receiver operating characteristic (ROC) curve was 0.82,meaning significant predictive values.The corresponding sensitivity and specificity for mean platelet volume (MPV) =10 fL were 70.0 ％ and 80.0 ％,respectively.Conclusions MPV in congenital heart defect patients with 22q11 is significantly higher than those without 22q11.It is an effective method for preliminary screening 22q11.Being obtained from full blood routine data,it is economic and quick.MPV =10 fL can be used as a cutoff for guidance for irradiated blood transfusion postoperatively.

Association of intercellular adhesion molecule-1 gene K469E polymorphism with chronic obstructive pulmonary disease / 中南大学学报(医学版)

OBJECTIVE@#To test the association of K469E, the common intercellular adhesion molecule-1 (ICAM-1) polymorphism with chronic obstructive pulmonary disease (COPD) and expression of ICAM-1 in Han people of Central and South Region in China.@*METHODS@#A case-control study was done on 91 patients with COPD and 80 matched controls of Han people from central and south region in China, mainly from Hunan Province. Genomic DNA was extracted from white blood cells. ICAM-1 sequences were amplified by PCRand analyzed by agarose gel electrophoresis. Genotypes were defined by base sequencing. In addition, soluable intercellular adhesion molecule-1 (sICAM-1) serum levels were measured in 86 people picked out randomly from the COPD group and the control group.@*RESULTS@#There was no difference in the frequency of the genotype and allele between the COPD group and the controls, but compared with those who were not very severe, the frequency of KE/ EE genotypes and E allele in COPD patients at very severe stage was significantly higher (10/16 vs 26/75, 12/30 vs 20/150, P0.05).@*CONCLUSION@#K469E polymorphism of ICAM-1 may not affect the susceptibility of COPD and the expression of ICAM-1 in Han people from central and south of China in this study, but carriers of E allele are at high risk of developing severe stage of COPD.