BackgroundSubtelomeric imbalance is widely accepted as related to developmental delay/mental retardation (DD/MR). Fine mapping of aberrations in gene-enriched subtelomeric regions provides essential clues for localizing critical regions, and provides a strategy for identifying new candidate genes. To date, no large-scale study has been conducted on subtelomeric aberrations in DD/MR patients in mainland China.MethodsThis study included 451 Chinese children with moderate to severe clinically unexplained DD/MR. The subtelomere-MLPA (multiplex ligation dependent probe amplification) and Affymetrix human SNP array 6.0 were used to determine the subtelomeric copy number variations. The exact size and the breakpoint of each identified aberration were well defined.ResultsThe submicroscopic subtelomeric aberrations were identified in 23 patients, with a detection rate of 5.1%. 16 patients had simple deletions, 2 had simple duplications and 5 with both deletions and duplications. The deletions involved 14 different subtelomeric regions (1p, 2p, 4p, 6p, 7p, 7q, 8p, 9p, 10p, 11q, 14q, 15q, 16p and 22q), and duplications involved 7 subtelomeric regions (3q, 4p, 6q, 7p, 8p, 12p and 22q). Of all the subtelomeric aberrations found in Chinese subjects, the most common was 4p16.3 deletion. The sizes of the deletions varied from 0.6 Mb to 12 Mb, with 5-143 genes inside. Duplicated regions were 0.26 Mb to 11 Mb, with 6-202 genes inside. In this study, four deleted subtelomeric regions and one duplicated region were smaller than any other previously reported, specifically the deletions in 11q25, 8p23.3, 7q36.3, 14q32.33, and the duplication in 22q13. Candidate genes inside each region were proposed.ConclusionsSubmicroscopic subtelomeric aberrations were detected in 5.1% of Chinese children with clinically unexplained DD/MR. Four deleted subtelomeric regions and one duplicated region found in this study were smaller than any previously reported, which will be helpful for further defining the candidate dosage sensitive gene associated with DD/MR.

BackgroundPrevious studies reported that patients with preexisting radiological interstitial lung abnormalities (ILAs) were more susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy (TRT). The present study aimed to evaluate the incidence and predictors of RP after TRT in patients with small-cell lung cancer (SCLC) with or without preexisting radiological ILAs.MethodsA total of 95 consecutive patients with SCLC between January 2015 and December 2015, who were treated with thoracic intensity-modulated radiation therapy at Shanghai Pulmonary Hospital,Tongji University School of Medicine, were analyzed. The diagnosis of ILAs was reviewed by two experienced thoracic radiologists based on the pretreatment high-resolution computed tomography imaging, such as honeycombing, subpleural reticular opacities, ground-glass opacity, and traction bronchiectasis. Univariate and multivariate analyses were used to assess the correlation of clinical factors, preexisting radiological ILAs, and dose-volume histogram-based dosimetric parameters with RP.ResultsFifteen (15.8%) patients had preexisting radiological ILAs. The incidence of ≥ grade 2 and 3 RP at 1 year was 27.1% and 12.7% in the entire cohort, respectively. Preexisting radiological ILAs were associated with an increased risk of ≥grade 2 RP (50.0% in ILAs + vs 23.3% in ILAs−, P = 0.017) and ≥ grade 3 RP (35.8% in ILAs + vs 8.9% in ILAs−, P = 0.005) at 1 year. Preexisting radiological ILAs and smoking history (≥40 pack-years of smoking) were significant predictors of ≥grade 3 RP in multivariate analysis (P = 0.023 and 0.012, respectively).ConclusionsPreexisting radiological ILAs and smoking history (≥40 pack-years of smoking) are associated with an increased risk of ≥grade 3 RP after TRT in patients with SCLC.

Tetrahydrobiopterin (BH(4)) deficiency is an autosomal recessive disorder caused by enzyme defects in the biosynthesis or recycling of BH(4). Patients with BH(4) deficiency present with severe neurological signs and symptoms and require a different treatment from classical phenylketonuria. During the last 12 years, 31 cases of BH(4) deficiency were identified in our department. They were all classified as 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. They were diagnosed at the ages of 2.5-48 months and treated with BH(4), L-dopa and 5-hydroxytryptophan immediately after diagnosis. The average development quotients (DQ) at diagnosis and after treatment for more than 3 years were 53+/- 16, and 78+/- 15, respectively. A significant negative correlation was observed between the level of the DQ and the age at which treatment was commenced (r = -0.751, p = 0.002). Developmental profiles were uneven. Language, adaptability and at later age mathematics were particularly weak areas. Only two patients achieved a good performance in mathematics. Eleven patients who were treated with drugs from ages of 2.9-48 months had neuroradiological scanning. Computed tomography disclosed calcification in lentiform nuclei in one patient and magnetic resonance imaging disclosed delayed myelination and abnormal high intensity signal in cerebral white matter in all of them. Even though most of abnormalities were reversible, small patchy or spotted areas were still present on these regions after treatment for 10-46 months. In summary, our study supports the substantial efficacy of the current therapeutic approach in PTPS deficiency of normalizing amine neurotransmitters with three drugs as early as possible. For the first time, calcifications could be detected in patients with PTPS deficiency. Abnormalities in white matter on magnetic resonance imaging were not related to clinical manifestations and most were reversible.

Pulmonary emphysema (PE) has been demonstrated to have a high prevalence in patients with locally advanced non-small cell lung cancer (NSCLC). A total of 153 patients with locally advanced NSCLC were enrolled in this study to investigate the association between PE and radiation pneumonitis (RP) after definitive thoracic radiation therapy (TRT). The incidence of RP in Grade 2, 3 and 5 were 11.1%, 9.8% and 0.7%, respectively. Univariate analysis revealed that age, PE, forced vital capacity (FVC), arterial partial pressure of oxygen (PO2) and mean lung dose (MLD) were significantly associated with the risk of Grade ≥2 or Grade ≥3 RP in patients with squamous cell carcinoma (SCC, P < 0.05). Logistic analysis demonstrated that PE was an independent risk factor of RP in SCC (P < 0.05). Receiver operating characteristics (ROC) analysis revealed that the combination of age, PE, FVC, PO2 and MLD had a higher value to predict RP in SCC (AUC = 0.856 in Grade ≥2 RP and 0.882 in Grade ≥3 RP, respectively). Kaplan-Meier analysis revealed that the more severe the PE, the higher the incidence of RP in SCC. Our results revealed that PE was a high risk factor for locally advanced NSCLC patients followed definitive TRT, especially for SCC patients.