ObjectiveTo identify 3 the disease-causing genes and mutations of Leber congenital amaurosis (LCA), and to study the correlation of phenotype and genotype. MethodsA retrospective study. Four LCA patients and seven family members who were diagnosed by eye examination in Ning Xia Eye Hospital of People's Hospital of Ningxia Hui Autonomous Region from January to December 2021 were included in the study. Four patients were from 3 unrelated families. Detailed collection of medical history and family history were received. Related ophthalmologic examination were collected and genomic DNA was extracted from peripheral blood. Whole-exome sequencing method was used for genetic diagnosis. The identified variant was confirmed with Sanger sequencing. Potential pathogenic mutation was analyzed using software and conserved domain analysis and performed co-separated analysis between the family member and the proband. ResultsOf the 4 patients, 1 patient was males and 3 patients were females; the age was from 4 to 18 years. Nystagmus were seen in 3 cases, finger pressing eyes and night blindness was seen in 1 cases; electroretinogram showed 4 cases of extinction or near extinction. The foveal reflection was visible in all eyes, and there was no obvious abnormality in the peripheral retina. One eye had strong reflection signal with raised ellipsoid in macular area; two eyes had weak reflection signal faintly visible between retinal layers; 1 eye had increased blood vessel branches, peripheral retinal non-perfusion area with capillary leakage; annular strong autofluorescence in macular area 4 eyes. No obvious abnormality was found in the phenotypes of family members. Genetic testing showed that the proband of pedigree 1 (Ⅱ-1) was found a homozygous missense mutation in c.640A>T (p.C214S) (M1) of PRPH2 gene. The proband of pedigree 2 (Ⅱ-2) was found compound heterozygous mutation in c.1256G>A(p.R419Q) (M2) and c.1A>C (p.M1L) (M3) of TULP1 gene. The proband 3 (Ⅱ-1) and her sister (Ⅱ-2) were both found compound heterozygous mutation in c.1943T>C (p.L648P) (M4) and c.380C>T (p.P127L) (M5) of GUCY2D gene. The parents and sister (Ⅱ-1) of the proband in family 2 and the parents of the proband in family 3 were all carriers of the corresponding heterozygous variant. M1, M3, M4, M5 were novel mutations and unreported. The genotype and disease phenotype were co-segregated within the family. According to the analysis of pedigree and genetic testing results, all 3 families were autosomal recessive inheritance. The amino acid conservation analysis found that M1, M2, M3, M4, and M5 were highly conserved among species. The results of bioinformatics analysis were all pathogenic variants. ConclusionsPRPH2 gene M1, TULP1 gene M3, and GUCY2D gene M4, M5 were novel mutations and not been reported in the literature and database. This research expanded the gene mutation spectrum of LCA. The patients with LCA have available characterristics, including onset age, varying ocular fundus and severe visual impairment.
ObjectiveTo explore risk factors associated with mortality and restenosis after the surgery for congenital pulmonary venous stenosis (CPVS) combined with congenital heart disease.MethodsFrom May 2007 to August 2019, 58 patients received surgical relief of CPVS combined with congenital heart disease, including 24 males and 34 females, aged 17.2±26.3 months, weighing 8.8±8.2 kg. Endpoints were death and restenosis, and the risk factors were analyzed. A univariate and multivariate risk analyses were performed.ResultsPreoperative pulmonary venous stenosis severity score (PVSSS) was 4.5±2.7. Average pulmonary vein counts with CPVS was 1.9±1.0. There were 2 (3.4%) early deaths. The mean follow-up time was 2-145 (49.8±40.0) months. The 1-, 2-, 3- and 5-year overall survival rates were 86.7%, 81.3%, 78.5% and 73.6%, respectively, and the pulmonary venous restenosis-free rates were 79.6%, 68.5%, 68.5% and 68.5%, respectively. Preterm birth was an independent risk factor for mortality. The pulmonary venous peak flow rate ≥1.2 m/s at discharge was an independent risk factor for mortality and restenosis.ConclusionThe prognosis of CPVS is still poor. Postoperative residual stenosis at discharge is an independent risk factor for death and restenosis.
Our country has made great progress in the surgical treatment of congenital heart disease, but after entering the new era, congenital cardiac surgery also presents some new features and trends. The quality of data of Guangdong congenital heart defects monitoring network was recognized by international organizations. We analyzed the data of the incidence of congenital heart disease, the rate of surgical treatment, the mortality of surgical procedures and the quality of surgical treatment in Guangdong province from Guangdong congenital heart defects monitoring network, and then accurately understood the development characteristics of congenital cardiac surgery. It is very helpful to clarify the regional status of congenital cardiac surgery, which is conducive to the development of a more reasonable surgical strategy for congenital heart disease, and finally promote the further development of congenital cardiac surgery in China.
Objective To evaluate the safety and mid- to long-term efficacy of surgical correction of isolated partial anomalous pulmonary venous connection (IPAPVC). Methods We retrospectively collected consecutive patients who were diagnosed with IPAPVC and underwent surgical correction at Fuwai Hospital of Chinese Academy of Medical Sciences and Fuwai Yunnan Cardiovascular Hospital from June 2009 to May 2019, summarized the basic preoperative and intraoperative data of patients, analyzed the postoperative and mid- to long-term follow-up results. Results A total of 54 patients were enrolled, including 29 males and 25 females, with an average age of 16.20±2.40 years, ranging from 1 month to 62 years. There were 28 (51.9%) patients with varying degrees of arrhythmia, 22 (40.7%) patients with cardiac insufficiency, and 39 (72.2%) patients with pulmonary hypertension. According to Bordy's typing, 14 (25.9%) patients were classified as type A, 23 (42.6%) type B, 4 (7.4%) type C, 5 (9.3%) type D and 8 (14.8%) mixed type. Transthoracic echocardiography was performed in the whole group of patients and the accuracy of staging diagnosis was 66.7% (36/54), and cardiac CT angiography (CTA) was performed in 37 patients and the accuracy of staging diagnosis was 94.6% (35/37). All surgical procedures were assisted with cardiopulmonary bypass, aortic cross-clamping time was 0-219 (67.02±5.23) min, cardiopulmonary bypass time was 40-261 (105.09±5.23) min, and there was no serious intraoperative complication. Postoperative tracheal intubation time was 0-230 (13.33±4.20) h, intensive care unit stay was 0-13 (1.89±0.28) days, postoperative hospital stay was 5-18 (7.20±0.38) days, and follow-up time was 16-140 (62.58±5.12) months. There were 2 (3.7%) all-cause postoperative deaths, including 1 in-hospital death and 1 death during the follow-up, and there was no intraoperative death. Among the survivors, there were 3 patients with surgery-related complications: 1 patient had atrial septal defect with the second surgical treatment, 1 early obstruction of the superior vena cava and 1 arrhythmia. Two patients had complications of IPAPVC (atrial fibrillation, collateral circulation) prior to surgery and underwent the second surgery with a poor prognosis, and 1 patient had preoperative cardiac insufficiency and atrial fibrillation, whose symptoms persisted for a long time during the follow-up. Conclusion IPAPVC accounts for a lower percentage of partial anomalous pulmonary venous connection, transthoracic echocardiography combined with CTA improves diagnostic accuracy, and IPAPVC should be treated with elective surgery after diagnosis. The surgical approach should be individualized with imaging features such as disease staging, number of drains and drainage location. Surgical treatment of IPAPVC is safe and effective, and regular follow-up is warranted.
Objective
To explore the value of extracorporeal membrane oxygenation(ECMO) combined with hypothermia therapy for children patients with refractory cardiac arrest after congenital heart disease surgery.
Methods
From January 2013 to June 2016, we conducted a prospective study of 23 children (18 males, 5 females at age of 7±11 months) who underwent ECMO for refractory cardiac arrest after congenital heart disease surgery. All patients were randomly divided into two groups: a standard group (11 patients) and a hypothermia group (12 patients). The patients of the standard group received standard therapy (the core body temperature maintaining at 37.0℃) and the hypothermia group received hypothermia therapy (the core body temperature maintaining at 33.0℃). The hospital discharge rate, the rate of weaning from ECMO and the morbidity were compared between the two groups.
Results
Eleven of 23 patients (47.8%) were weaned from ECMO successfully and 7 of 23 patients (30.4%) discharged from hospital. The hospital discharge rate between the hypothermia group (n=6, 50.0%) and the standard group (n=1, 9.1%) had no statistical difference (χ2=4.537, P=0.069). The rate of weaning from ECMO of the hypothermia group (n=9, 75.0%) was higher than that of the standard group (n=2, 18.2%, χ2=7.425, P=0.006). The morbidity between the two groups had no statistical difference.
Conclusion
Extracorporeal cardiopulmonary resuscitation can improve the survival rate of the children who suffered from refractory cardiac arrest after congenital heart disease surgery. There is no evidence that ECMO combined with hyperthermia therapy is better than the only ECMO in improving the discharge rate. But ECMO combined with hypothermia therapy has higher rate of weaning from ECMO than that of the only ECMO.
Objective To investigate the morphological anatomical abnormal ities of high congenital dislocation of hip in adults and provide anatomical basis for the total hip arthroplasty (THA). Methods From May 1997 to July 2008, 49 patients (57 hi ps) with high congenital dislocation of hip (Hartofilakidis type III) were treated. There were 6 males and 43 females with an average age of 29.4 years old (18-56 years old). The locations were left in 24 hi ps and right in 33 hi ps. The morphological parameters (including femoral length, isthmus, height of femoral head center, neck-shaft angle, medialhead offset, anteversion angle, canal flare index, anteroposterior diameter of the true acetabulum, posterior thickness of the true acetabulum, depth of the true acetabulum) of suffering hips (dislocation group, n=57) were measured by preoperative X-ray, CT and intraoperative cl inical observation and were compared with those of contralateral hips (control group, n=41). The intraoperative situations of hip were observed. Results The height of dislocation was (45.41 ± 2.15) mm. The length difference of both lower extremities was (40.41 ± 2.02) mm. In dislocation group, isthmus was shortened; height of femoral head center, neck-shaft angle and medial head offset were decreased; and anteversion angle was increased. CT showed that the canal flare index was larger than 4.7, femoral shape was funnel-shaped according to Noble classification. Anteroposterior diameter of the true acetabulum became smaller, posterior thickness of the true acetabulum became thicker, and depth of the true acetabulum was shallower. There were statistically significant differences in the morphological parameters of femur and acetabulum between two groups (P lt; 0.05). The intraoperative measurements showed that the anteroposterior diameter of acetabulum was (32.98 ± 1.02) mm and the depth of acetabulum was (14.21 ± 0.56) mm. There was no statistically significant difference between intraoperative measurements and preoperative measurements (P gt; 0.05). The acetabulum was full of fat and fibrous tissues. Running of the sciatic nerve in 40 cases were changed and it ran upward and laterally. Conclusion When high congenital dislocation of the hip in adults is treated with THA, anatomical variation must be fully taken into account. The acetabulum is expanded toward posterosuperior, excessive reamed should be avoided to prevent femoral fractures, and appropriate or tailor-made prosthesis was selected.
Objective To explore the treatment method of congenital heart disease (CHD) with pulmonary artery hypertension (PAH) in infants with Down syndrome (DS). Methods The clinical data of 60 CHD patients with PAH from March 2015 to August 2016 in our hospital were retrospectively analyzed. There were 30 infants with DS classified as a DS group (trial group, 17 males and 13 females with a mean age of 1.15±0.25 years) and the other 30 patients without DS were classified as a control group (20 males and 10 females with a mean age of 1.24±0.30 years). All the patients underwent surgical treatment and fasudil combined with sildenafil were used to prevent pulmonary hypertension crisis postoperatively. Results There was no significant difference in cardiopulmonary bypass time, aortic cross-clamping time, modified ultrafiltration time and the incidence of postoperative respiratory complications between the two groups. The pulmonary systolic blood pressure significantly decreased at 24 h after operation in the two groups (both P<0.05). The arterial oxygen pressure and oxygenation index of the trial group were lower than those of the control group at 6 h after operation (both P<0.05). The mechanical ventilation time and intensive care time of the trial group were significantly longer than those of the control group (P=0.007 and P=0.000, respectively). There were no reoperations or early death. Conclusion The effects of surgical repair of CHD with PAH in infants with DS are satisfactory by grasping the indication, protecting lung function and controlling PAH in the early postoperative period, although there is a high incidence of pulmonary complications.
Stargardt disease (STGD) is an inherited disorder of retinal pigment epithelium. Three genes have been found to be implicated in STGD including Abca4 (adenosine triphosphate-binding cassette, sub-family A, member 4), Elovl4 (elongation of very long chain fatty acids protein 4) and Prom1 (prominin-1). Target genes can be delivered to the retina by various methods such as lentivirus (LV) vectors, adeno-associated virus (AAV) vectors and non-viral nano-particles. The Abca4-/-, Elovl4-/- and Prom1-/- mice model are used to study the pathogenesis mechanism and treatment of STGD. Retinal function improved significantly upon gene therapy in these models. Based on these works using animal model, phase Ⅰ/Ⅱa clinical trial of Abca4-associated STGD gene therapy are underway. AsaLV vector, equine infectious anemia virus (EIAV) is used to carry the Abca4 gene. These studies will evaluate three dose levels of the EIAV vector for safety, tolerability and biological activity. Moreover, some preclinical attempts to deliver Abca4 via AAV have been made usingamodified AAV vectors because of the large size of the ABCA4 cDNA. The good responses in animal models render STGDavery attractive object for human gene therapy after the successful of the phase Ⅰ/Ⅱ clinical trials of Leber′s congenital amaurosis.
Objective To analyze the pathogenesy and mutation of X-linked juvenile retinoschisis (XLRS) 1 gene in XLRS families, and to provide the theory basis in directing gene diagnosis. Methods The mutation of XLRS1 gene code in two XLRS families were detected and screened by polymerase chain reaction (PCR) and DNA direct sequence determination. Results Pro193Ser mutation was detected in family 1. Conclusion Pro193Ser mutation could be found in XLRS families, which can be used for genetic consultation and prenatal gene diagnosis. (Chin J Ocul Fundus Dis，2004，20：149-151)
ObjectiveTo investigate the diagnosis and treatment of thumb polydactyly with symphalangism in children.MethodsSeven cases of thumb polydactyly with symphalangism were treated between January 2013 and May 2017. There were 5 males and 2 females, aged from 10 months to 11 years, with an average age of 3.1 years. The thumb-polydactyly was diagnosed with MRI and it was seen that the base of radial multi-finger and the proximal phalangeal joint were connected by cartilage. All patients were treated with resection, lateral collateral ligament reconstruction, bone osteotomy and internal fixation.ResultsThe operation was successfully completed, and there was no early complications such as infection and flap necrosis. All patients were followed up 6-23 months (mean, 14.1 months). At last follow-up, there was no deformity finger, scar contracture, and other complications. The extension of the interphalangeal joint was no limited, and the flexion range of the interphalangeal joint was 20-75° (mean, 56.7°). The appearance and function of the thumb was rated as excellent in 3 cases and good in 4 cases by Japanese Society for Surgery of the Hand (JSSH) scoring, with the excellent and good rate of 100%.ConclusionThe thumb polydactyly with symphalangism in children can be combined with clinical manifestations, X-ray film, and MRI examination to diagnose, and can obtain satisfactory results through the reconstruction of lateral collateral ligament, bone osteotomy, and internal fixation.
