Research suggests that the prevalence of obesity in children with autism spectrum disorder (ASD) is at least as high as that seen in typically developing children. Many of the risk factors for children with ASD are likely the same as for typically developing children, especially within the context of today's obesogenic environment. The particular needs and challenges that this population faces, however, may render them more susceptible to the adverse effects of typical risk factors, and they may also be vulnerable to additional risk factors not shared by children in the general population, including psychopharmacological treatment, genetics, disordered sleep, atypical eating patterns, and challenges for engaging in sufficient physical activity. For individuals with ASD, obesity and its sequelae potentially represent a significant threat to independent living, self-care, quality of life, and overall health.
Concentrations of lead (Pb) in breast milk (PbM) and blood (PbB) were measured in a current cohort of lactating mothers living in Andean communities where women of childbearing age engage in the occupational use of Pb, and compared to results obtained in earlier studies. Mean PbM concentration in the current group of breastfeeding mothers tested in 2012/2013 was 3.73 mug/L (SD: 7.3; range: 0.049-28.04), and significantly lower than the 9.83 mug/L (SD: 12.75; range: 0.2-49) previously observed in breastfeeding mothers in the study area from 1999 to 2007. Breastfeeding women in the current cohort showed an average PbM/PbB ratio of 3.6%, which is in agreement with other studies. The mean PbB level obtained for the current cohort was 7.8 mug/dl (SD: 5.2; range: 1.4-21), and significantly lower than the mean PbB level of 20.8 mug/dl (SD: 16.4; range: 4-73) obtained for the comparison group of breastfeeding mothers tested between 1999 and 2007. A correlation of .687 between paired PbM and maternal PbB was found, indicating that maternal PbB level is a significant predictor of PbM. Current PbM levels remain higher than international averages, but indicate that maternal Pb exposure has declined over time in the environmentally Pb-contaminated study area. The current reduction in Pb in milk and blood of breastfeeding mothers may be due to adherence to a Pb-exposure education and prevention program initiated by the authors in the study area years earlier, as well as recent improvements in local health care delivery.
A comparison of food refusal related to characteristics of food in children with autism spectrum disorder and typically developing children
Parents of children with autism spectrum disorder (ASD) frequently report child food refusal based on characteristics of food. Our study sought to determine whether parent report of food refusal based on the characteristics of food was greater in children with ASD than in typically developing children, associated with a greater percentage of foods refused of those offered, and associated with fruit and vegetable intake. A modified food frequency questionnaire was used to determine overall food refusal as well as fruit and vegetable intake. Parent-reported food refusal related to characteristics of food (eg, texture/consistency, temperature, brand, color, shape, taste/smell, foods mixed together, or foods touching other foods) was compared between 53 children with ASD and 58 typically developing children aged 3 to 11 years in the Children's Activity and Meal Patterns Study (2007-2008). Children with ASD were significantly more likely to refuse foods based on texture/consistency (77.4% vs 36.2%), taste/smell (49.1% vs 5.2%), mixtures (45.3% vs 25.9%), brand (15.1% vs 1.7%), and shape (11.3% vs 1.7%). No differences between groups were found for food refusal based on temperature, foods touching other foods, or color. Irrespective of ASD status, the percentage of foods refused of those offered was associated with parent reports of food refusal based on all characteristics examined, except temperature. Food refusal based on color was inversely associated with vegetable consumption in both groups. Routine screening for food refusal among children with ASD is warranted to prevent dietary inadequacies that may be associated with selective eating habits. Future research is needed to develop effective and practical feeding approaches for children with ASD. All rights reserved.
Full issue of Volume 1, Issue 1 (March 2015) of the Journal of Global Radiology. Articles are available individually at http://escholarship.umassmed.edu/jgr/vol1/iss1/.
Rwanda is an equatorial country in central Africa (Figure 1), and part of the East African Community of Burundi, Kenya, Uganda and Tanzania. It is a small country, just over 10,000 square miles. Its population of nearly 12,000,000 makes it the most densely populated state in continental Africa. Rwanda’s capital, Kigali, is a mile-high city. Its elevation makes the climate much cooler and more comfortable than a typical equatorial climate. The average annual temperature is 20.5 degrees Celsius with a narrow range – April, the coldest month has an average temperature of 20 degrees, whereas August, the warmest month has an average temperature of 21.5 degrees. Economically, Rwanda functions as a subsistence agricultural country but has been actively striving to emerge as a middle-income country. Its primary exports are coffee and tea.
In 1994, the majority Hutu population carried out mass genocide of the ethnic Tutsi minority In a coordinated slaughter committed by neighbors against each other, and with low-technology weapons like machetes, nearly 1,000,000 people were killed in 100 days (1). The country was devastated. Immediately post-genocide, Rwanda was one of the poorest countries in the world with nearly 70% of the population living below the poverty line (2). Until 1997, Rwanda had the lowest life expectancy of any country in the world (3). The physician work force was depleted due to the direct and indirect consequences of the Rwandan Genocide. Since this time there has been a steady economic recovery (4), along with remarkable medical recovery. Average life expectancy nationwide, only 27 years in the early 1990s, has now reached 63 years (3).
Since the 2012 publication (5) highlighting its advances, radiology in Rwanda has benefitted from the capital infusion that has helped to propel the overall growth in the economic and health sectors. As of 2012, there are five national referral hospitals, 41 district hospitals, one military hospital and 451 health centers (6). The health centers are staffed primarily by nurses, while the district hospitals are staffed by general practitioners (graduates of medical school without a post-graduate education). Of the 625 total physicians in the country in 2011, 150 had completed residency (3).
Lisa Palmer, Institutional Repository Librarian at UMass Medical School, has developed excellent outreach strategies for working with faculty on grant-funded research support, including data management. In particular, she’ll discuss how she and her colleagues have leveraged the institutional repository in a collaboration with the UMass Center for Clinical and Translational Science on an NIH grant, and to support a Women’s Health Research grant from the National Library of Medicine.
Presentation for the ACRL 2015 bepress IR All-Star Tailgate event in Portland, OR, on March 25, 2015.
DAG-searched and Density-based Initial Centroid Location Method for Fuzzy Clustering of Big Biomedical Data
Randomly allocating initial centroids may lead to undesired steady states for fuzzy c-means (FCM) clustering. This paper proposes an alternative method to automatically search initial centroid location based on data density. Specifically, this method auto-searches points located in high-density domains as centroids using directed acycline graph (DAG) based algorithm, and then iteratively fnding the optimal patterns. Compared with random initialization method, our method seems to have the potential to improve FCM accuracy for larger data size with seconds' tradeoff in computational time using published datasets.
Energy, fatigue, or both? A bifactor modeling approach to the conceptualization and measurement of vitality
PURPOSE: Vitality is an important domain reflecting both the physical and emotional components of health-related quality of life. Because of its complexity, it has been defined and measured both broadly and narrowly. We explored the dimensionality of a very comprehensive item bank hypothesized to measure vitality and its related concepts.
METHODS: Secondary analyses were conducted using the responses of 1,343 adults representative of the US general population to Internet-based surveys including 42 items compiled from multiple scales (e.g., SF-36 Vitality, PROMIS-Fatigue), covering a broad range of vitality-related content areas (energy, fatigue, and their interference with physical, mental, social activities, and quality of life). Exploratory and confirmatory factor models were evaluated independently using split-half samples. Bifactor model was used to assess the essential unidimensionality of the items, in comparison with traditional unidimensional, multidimensional, and hierarchical models. Method effects of a common scale or phrase were modeled via correlating errors.
RESULTS: The exploratory factor analysis identified one dominant factor. The confirmatory factor analysis identified a best-fitting (CFI = 0.964, RMSEA = 0.084) bifactor model with one general (vitality) and two group (energy and fatigue) factors, explaining 69, 3, and 4 % of total variance. Correlating errors accounting for the method effects were important in identifying the substantive dimensionality of the items.
CONCLUSIONS: The bifactor model proved to be useful for evaluating the dimensionality of a complex construct. Results supported conceptualizing and measuring vitality as a unidimensional energy-fatigue construct. We encourage future studies comparing practical implications of measures based on the broader and narrower conceptualizations of vitality.
Comment on: Functional disability and cognitive impairment after hospitalization for myocardial infarction and stroke. [Circ Cardiovasc Qual Outcomes. 2014]
Healthy lifestyle and decreasing risk of heart failure in women: the Women's Health Initiative observational study
BACKGROUND: The impact of a healthy lifestyle on risk of heart failure (HF) is not well known.
OBJECTIVES: The objectives of this study were to evaluate the effect of a combination of lifestyle factors on incident HF and to further investigate whether weighting each lifestyle factor has additional impact.
METHODS: Participants were 84,537 post-menopausal women from the WHI (Women's Health Initiative) observational study, free of self-reported HF at baseline. A healthy lifestyle score (HL score) was created wherein women received 1 point for each healthy criterion met: high-scoring Alternative Healthy Eating Index, physically active, healthy body mass index, and currently not smoking. A weighted score (wHL score) was also created in which each lifestyle factor was weighted according to its independent magnitude of effect on HF. The incidence of hospitalized HF was determined by trained adjudicators using standardized methodology.
RESULTS: There were 1,826 HF cases over a mean follow-up of 11 years. HL score was strongly associated with risk of HF (multivariable-adjusted hazard ratio [HR] [95% confidence interval (CI)] 0.49 [95% CI: 0.38 to 0.62], 0.36 [95% CI: 0.28 to 0.46], 0.24 [95% CI: 0.19 to 0.31], and 0.23 [95% CI: 0.17 to 0.30] for HL score of 1, 2, 3, and 4 vs. 0, respectively). The HL score and wHL score were similarly associated with HF risk (HR: 0.46 [95% CI: 0.41 to 0.52] for HL score; HR: 0.48 [95% CI: 0.42 to 0.55] for wHL score, comparing the highest tertile to the lowest). The HL score was also strongly associated with HF risk among women without antecedent coronary heart disease, diabetes, or hypertension.
CONCLUSIONS: An increasingly healthy lifestyle was associated with decreasing HF risk among post-menopausal women, even in the absence of antecedent coronary heart disease, hypertension, and diabetes. Weighting the lifestyle factors had minimal impact. Elsevier Inc. All rights reserved.
Longitudinal association of anthropometric measures of adiposity with cardiometabolic risk factors in postmenopausal women
PURPOSE: Some studies suggest that anthropometric measures of abdominal obesity may be superior to body mass index (BMI) for the prediction of cardiometabolic risk factors; however, most studies have been cross-sectional. Our aim was to prospectively examine the association of change in BMI, waist-to-hip ratio (WHR), waist circumference (WC), and waist circumference-to-height ratio (WCHtR) with change in markers of cardiometabolic risk in a population of postmenopausal women.
METHODS: We used a subsample of participants in the Women's Health Initiative aged 50 to 79 years at entry with available fasting blood samples and anthropometric measurements obtained at multiple time points over 12.8 years of follow-up (n = 2672). The blood samples were used to measure blood glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides at baseline, and at years 1, 3, and 6. We conducted mixed-effects linear regression analyses to examine associations at baseline and longitudinal associations between change in anthropometric measures and change in cardiometabolic risk factors, adjusting for covariates.
RESULTS: In longitudinal analyses, change in BMI, WC, and WCHtR robustly predicted change in cardiometabolic risk, whereas change in WHR did not. The strongest associations were seen for change in triglycerides, glucose, and HDL-C (inverse association).
CONCLUSION: Increase in BMI, WC, and WCHtR strongly predicted increases in serum triglycerides and glucose, and reduced HDL-C. WC and WCHtR were superior to BMI in predicting serum glucose, HDL-C, and triglycerides. WCHtR was superior to WC only in predicting serum glucose. BMI, WC, and WCHtR were all superior to WHR.
Variations in the implementation of acute care surgery: results from a national survey of university-affiliated hospitals
BACKGROUND: To date, no studies have reported nationwide adoption of acute care surgery (ACS) or identified structural and/or process variations for the care of emergency general surgery (EGS) patients within such models.
METHODS: We surveyed surgeons responsible for EGS coverage at University Health Systems Consortium hospitals using an eight-page postal/e-mail questionnaire querying respondents on hospital and EGS structure/process measures. Survey responses were analyzed using descriptive statistics, univariate comparisons, and multivariable regression models.
RESULTS: Of 319 potential respondents, 258 (81%) completed the surveys. A total of 81 hospitals (31%) had implemented ACS, while 134 (52%) had a traditional general surgeon on-call (GSOC) model. Thirty-eight hospitals (15%) had another model (hybrid). Larger-bed, university-based, teaching hospitals with Level 1 trauma center verification status located in urban areas were more likely to have adopted ACS. In multivariable modeling, hospital type, setting, and trauma center verification predicted ACS implementation. EGS processes of care varied, with 28% of the GSOC hospitals having block time versus 67% of the ACS hospitals (p < 0.0001), 45% of the GSOC hospitals providing ICU [intensive care unit] care to EGS patients in a surgical/trauma ICU versus 93% of the ACS hospitals (p < 0.0001), 5.7 +/- 3.2 surgeons sharing call at GSOC hospitals versus 7.9 +/- 2.3 surgeons at ACS hospitals (p < 0.0001), and 13% of the GSOC hospitals requiring in-house EGS call versus 75% of the ACS hospitals (p < 0.0001). Among ACS hospitals, there were variations in patient cohorting (EGS patients alone, 25%; EGS + trauma, 21%; EGS + elective, 17%; and EGS + trauma + elective, 30%), data collection (26% had prospective EGS registries), patient hand-offs (56% had attending surgeon presence), and call responsibilities (averaging 4.8 +/- 1.3 calls per month, with 60% providing extra call stipend and 40% with no postcall clinical duties).
CONCLUSION: The potential of the ACS on the national crisis in access to EGS care is not fully met. Variations in EGS processes of care among adopters of ACS suggest that standardized criteria for ACS implementation, much like trauma center verification criteria, may be beneficial.
An observational study of social and emotional support in smoking cessation Twitter accounts: content analysis of tweets
BACKGROUND: Smoking continues to be the number one preventable cause of premature death in the United States. While evidence for the effectiveness of smoking cessation interventions has increased rapidly, questions remain on how to effectively disseminate these findings. Twitter, the second largest online social network, provides a natural way of disseminating information. Health communicators can use Twitter to inform smokers, provide social support, and attract them to other interventions. A key challenge for health researchers is how to frame their communications to maximize the engagement of smokers.
OBJECTIVE: Our aim was to examine current Twitter activity for smoking cessation.
METHODS: Active smoking cessation related Twitter accounts (N=18) were identified. Their 50 most recent tweets were content coded using a schema adapted from the Roter Interaction Analysis System (RIAS), a theory-based, validated coding method. Using negative binomial regression, the association of number of followers and frequency of individual tweet content at baseline was assessed. The difference in followership at 6 months (compared to baseline) to the frequency of tweet content was compared using linear regression. Both analyses were adjusted by account type (organizational or not organizational).
RESULTS: The 18 accounts had 60,609 followers at baseline and 68,167 at 6 months. A total of 24% of tweets were socioemotional support (mean 11.8, SD 9.8), 14% (mean 7, SD 8.4) were encouraging/engagement, and 62% (mean 31.2, SD 15.2) were informational. At baseline, higher frequency of socioemotional support and encouraging/engaging tweets was significantly associated with higher number of followers (socioemotional: incident rate ratio [IRR] 1.09, 95% CI 1.02-1.20; encouraging/engaging: IRR 1.06, 95% CI 1.00-1.12). Conversely, higher frequency of informational tweets was significantly associated with lower number of followers (IRR 0.95, 95% CI 0.92-0.98). At 6 months, for every increase by 1 in socioemotional tweets, the change in followership significantly increased by 43.94 (P = .027); the association was slightly attenuated after adjusting by account type and was not significant (P = .064).
CONCLUSIONS: Smoking cessation activity does exist on Twitter. Preliminary findings suggest that certain content strategies can be used to encourage followership, and this needs to be further investigated.
Testing item response theory invariance of the standardized Quality-of-life Disease Impact Scale (QDIS) in acute coronary syndrome patients: differential functioning of items and test
PURPOSE: The Quality-of-life (QOL) Disease Impact Scale (QDIS(R)) standardizes the content and scoring of QOL impact attributed to different diseases using item response theory (IRT). This study examined the IRT invariance of the QDIS-standardized IRT parameters in an independent sample.
METHOD: The differential functioning of items and test (DFIT) of a static short-form (QDIS-7) was examined across two independent sources: patients hospitalized for acute coronary syndrome (ACS) in the TRACE-CORE study (N = 1,544) and chronically ill US adults in the QDIS standardization sample. "ACS-specific" IRT item parameters were calibrated and linearly transformed to compare to "standardized" IRT item parameters. Differences in IRT model-expected item, scale and theta scores were examined. The DFIT results were also compared in a standard logistic regression differential item functioning analysis.
RESULTS: Item parameters estimated in the ACS sample showed lower discrimination parameters than the standardized discrimination parameters, but only small differences were found for thresholds parameters. In DFIT, results on the non-compensatory differential item functioning index (range 0.005-0.074) were all below the threshold of 0.096. Item differences were further canceled out at the scale level. IRT-based theta scores for ACS patients using standardized and ACS-specific item parameters were highly correlated (r = 0.995, root-mean-square difference = 0.09). Using standardized item parameters, ACS patients scored one-half standard deviation higher (indicating greater QOL impact) compared to chronically ill adults in the standardization sample.
CONCLUSION: The study showed sufficient IRT invariance to warrant the use of standardized IRT scoring of QDIS-7 for studies comparing the QOL impact attributed to acute coronary disease and other chronic conditions.
Quadrimodal distribution of death after trauma suggests that critical injury is a potentially terminal disease
BACKGROUND: Patterns of death after trauma are changing due to advances in critical care. We examined mortality in critically injured patients who survived index hospitalization.
METHODS: Retrospective analysis of adults admitted to a Level-1 trauma center (1/1/2000-12/31/2010) with critical injury was conducted comparing patient characteristics, injury, and resource utilization between those who died during follow-up and survivors.
RESULTS: Of 1,695 critically injured patients, 1,135 (67.0%) were discharged alive. As of 5/1/2012, 977/1,135 (86.0%) remained alive; 75/158 (47.5%) patients who died during follow-up, died in the first year. Patients who died had longer hospital stays (24 vs. 17 days) and ICU LOS (17 vs. 8 days), were more likely to undergo tracheostomies (36% vs. 16%) and gastrostomies (39% vs. 16%) and to be discharged to rehabilitation (76% vs. 63%) or skilled nursing (13% vs. 5.8%) facilities than survivors. In multivariable models, male sex, older age, and longer ICU LOS predicted mortality. Patients with ICU LOS >16 days had 1.66 odds of 1-year mortality vs. those with shorter ICU stays.
CONCLUSIONS: ICU LOS during index hospitalization is associated with post-discharge mortality. Patients with prolonged ICU stays after surviving critical injury may benefit from detailed discussions about goals of care after discharge.
OBJECTIVE: To test the hypothesis that greater chocolate-candy intake is associated with more weight gain in postmenopausal women.
METHODS: A prospective cohort study involved 107,243 postmenopausal American women aged 50-79 years (mean = 60.7) at enrollment in the Women's Health Initiative, with 3-year follow-up. Chocolate-candy consumption was assessed by food frequency questionnaire, and body weight was measured. Linear mixed models, adjusted for demographic, socio economic, anthropomorphic, and behavioral variables, were used to test our main hypotheses.
RESULTS: Compared with women who ate a 1 oz ( approximately 28 g) serving of chocolate candy < 1 per month, those who ate this amount 1 per month to < 1 per week, 1 per week to < 3 per week and > =3 per week showed greater 3-year prospective weight gains (kg) of 0.76 (95% CI: 0.66, 0.85), 0.95 (0.84, 1.06), and 1.40 (1.27, 1.53), respectively, (P for linear trend < 0.0001). Each additional 1 oz/day was associated with a greater 3-year weight gain (kg) of 0.92 (0.80, 1.05). The weight gain in each chocolate-candy intake level increased as BMI increased above the normal range (18.5-25 kg/m(2) ), and was inversely associated with age.
CONCLUSIONS: Greater chocolate-candy intake was associated with greater prospective weight gain in this cohort of postmenopausal women.
Lessons Learned from the Development and Implementation of Two Internet-enhanced Culturally Relevant Physical Activity Interventions for Young Overweight African-American Women
This research team has designed and implemented 2 culturally relevant, Internet-enhanced physical activity (PA) interventions for overweight/obese African-American female college students. Presumably, these are the only prospectively designed, culturally relevant interventions using the Internet to promote PA among African-American women. Due to the limited research on this topic, the experiences associated the design and implementation of these studies were syntesized and 5 key lessons learned from this research were formulated. Findings provide insight for researchers to consider when developing Internet-based PA promotion interventions for African-American women. Lessons learned included: 1) Elicit and incorporate feedback from the target population throughout development of an Internet-based PA promotion tool; 2) Incorporate new and emerging technologies into Internet-enhanced PA programs; 3) Maintain frequent participant contact and provide frequent incentives to promote participant engagement; 4) Supplement Internet-based efforts with face-to-face interactions; 5) Include diverse images of African-American women and culturally relevant PA-related information in Internet-based PA promotion materials.
Thirty day hospital re-admissions in patients with non ST-segment elevation acute myocardial infarction
BACKGROUND: Limited data exist about relatively recent trends in the magnitude and characteristics of patients who are rehospitalized shortly after admission for a non ST-segment elevation acute myocardial infarction (NSTEMI). This observational study describes decade-long trends (1999-2009) in the magnitude and characteristics of patients readmitted to the hospital within 30 days of hospitalization for an incident (initial) episode of NSTEMI.
METHODS: We reviewed the medical records of 2,249 residents of the Worcester (MA) metropolitan area who were hospitalized for an initial NSTEMI in 6 biennial periods between 1999 and 2009 at 3 central MA medical centers.
RESULTS: The average age of our study population was 72 years, 90% were white, and 46% were women. The proportion of patients who were readmitted to the hospital for any cause within 30 days after discharge for a NSTEMI remained unchanged between 1999 and 2009 (approximately 15%) in both crude and multivariable adjusted analyses. Slight declines were observed for cardiovascular disease-related 30-day readmissions over the ten-year study period. Women, elderly patients, those with multiple chronic comorbidities, a prolonged index hospitalization, and patients who developed heart failure during their index hospitalization were at higher risk for being readmitted within 30-days than respective comparison groups.
CONCLUSIONS: Thirty day hospital readmission rates after hospital discharge for a first NSTEMI remained stable between 1999 and 2009. We identified several groups at higher risk for hospital readmission in whom further surveillance efforts and/or tailored educational and treatment approaches remain needed.
Diet quality and history of gestational diabetes mellitus among childbearing women, United States, 2007-2010
INTRODUCTION: Women with a history of gestational diabetes mellitus (GDM) have elevated risk of developing type 2 diabetes. Diet quality plays an important role in the prevention of type 2 diabetes. We compared diet quality among childbearing women with a history of GDM with the diet quality of childbearing women without a history of GDM.
METHODS: We used data from the National Health and Nutrition Examination Survey for 2007 through 2010. We included women without diabetes aged 20 to 44 years whose most recent live infant was born within the previous 10 years and who completed two 24-hour dietary recalls. The Healthy Eating Index (HEI)-2010 estimated overall and component diet quality. Multivariable linear regression models estimated the association between a history of GDM and current diet quality, adjusting for age, education, smoking status, and health risk for diabetes.
RESULTS: A history of GDM was reported by 7.7% of women. Compared with women without a history of GDM, women with a history of GDM had, on average, 3.4 points lower overall diet quality (95% confidence interval [CI], -6.6 to -0.2) and 0.9 points lower score for consumption of green vegetables and beans (95% CI, -1.4 to -0.4). Other dietary component scores did not differ by history of GDM.
CONCLUSION: In the United States, women with a history of GDM have lower diet quality compared with women who bore a child and do not have a history of GDM. Improving diet quality may be a strategy for preventing type 2 diabetes among childbearing women.
Whole-exome sequencing identifies tetratricopeptide repeat domain 7A (TTC7A) mutations for combined immunodeficiency with intestinal atresias
BACKGROUND: Combined immunodeficiency with multiple intestinal atresias (CID-MIA) is a rare hereditary disease characterized by intestinal obstructions and profound immune defects.
OBJECTIVE: We sought to determine the underlying genetic causes of CID-MIA by analyzing the exomic sequences of 5 patients and their healthy direct relatives from 5 unrelated families.
METHODS: We performed whole-exome sequencing on 5 patients with CID-MIA and 10 healthy direct family members belonging to 5 unrelated families with CID-MIA. We also performed targeted Sanger sequencing for the candidate gene tetratricopeptide repeat domain 7A (TTC7A) on 3 additional patients with CID-MIA.
RESULTS: Through analysis and comparison of the exomic sequence of the subjects from these 5 families, we identified biallelic damaging mutations in the TTC7A gene, for a total of 7 distinct mutations. Targeted TTC7A gene sequencing in 3 additional unrelated patients with CID-MIA revealed biallelic deleterious mutations in 2 of them, as well as an aberrant splice product in the third patient. Staining of normal thymus showed that the TTC7A protein is expressed in thymic epithelial cells, as well as in thymocytes. Moreover, severe lymphoid depletion was observed in the thymus and peripheral lymphoid tissues from 2 patients with CID-MIA.
CONCLUSIONS: We identified deleterious mutations of the TTC7A gene in 8 unrelated patients with CID-MIA and demonstrated that the TTC7A protein is expressed in the thymus. Our results strongly suggest that TTC7A gene defects cause CID-MIA. Mosby, Inc. All rights reserved.