scholarly journals SAT-289 Evidence That Combined Pituitary Hormone Deficiency Frequently Has a Digenic/Oligogenic Etiology

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Youn Hee Jee ◽  
Mariam Gangat ◽  
Olga Yeliosof ◽  
Adrian Temnycky ◽  
Selena Vanapruks ◽  
...  
Keyword(s):  
Family History ◽  
De Novo ◽  
Snp Array ◽  
De Novo Mutation ◽  
Control Group ◽  
Pituitary Hormone ◽  
Monogenic Inheritance ◽  
Pituitary Disease ◽  
History Of ◽  
Congenital Hypopituitarism

Abstract Congenital hypopituitarism usually occurs in a child without a family history of pituitary disease. Explanations for such sporadic occurrence include: 1) monogenic inheritance (recessive or de novo), 2) digenic/oligogenic inheritance, and/or 3) nongenetic factors. To help distinguish these possibilities, we studied 9 children with hypopituitarism (HP)(small anterior pituitary gland, ectopic posterior pituitary, and either isolated GH deficiency (n=1) or combined with other pituitary hormone deficiencies(n=8)), with non-consanguineous parents and no family history of pituitary disease. SNP array analyses confirmed paternity and non-consanguinity and excluded significant copy-number variation. Exome sequencing was performed in probands and parents. Candidate variants (coverage >10, confirmed by examining BAM files, population frequency <1%, <2 homozygous subjects in gnomAD, and pathogenic prediction by at least 2 out of 3 prediction algorithms (SIFT, MutationTaster, PolyPhen2)) were identified. Children with non-familial non-endocrine idiopathic short stature (ISS) (n=19, sequenced at the same laboratory followed by simultaneous data processing with HP patients), served as a control group. To assess the frequency of genetic (mono-, di-, or oligogenic) HP cases, we identified heterozygous variants (regardless of inheritance) in 42 genes previously reported to be associated with pituitary development. The average number of variants per proband was greater in HP than in ISS (1.1 vs 0.26, P = 0.04). Similarly, the number of probands with at least 1 variant in a pituitary-associated gene was greater in HP than in ISS (67% vs 21%, P = 0.035). These data suggest that sporadic hypopituitarism is frequently genetic. To assess the number of monogenic cases, we counted the number of candidate variants (in any gene in the genome, to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence with a monogenic etiology (de novo mutation, autosomal recessive, X-linked recessive). There were fewer monogenic candidates in subjects with HP than ISS (1.6 vs 2.6 candidates/proband, P = 0.03). These data are consistent with approximately 1.6 non-causative variants/proband in both groups plus approximately 1 causative monogenic variant in ISS vs approximately 0 causative monogenic variants in HP. Candidate variants in genes previously reported to explain the phenotype were identified in 0 out of 9 trios with HP and in 8 of 19 trios with ISS (42%). These findings suggest that a monogenic inheritance is less common in HP than in ISS. In conclusion, the findings suggest that sporadic congenital hypopituitarism is frequently genetic but infrequently monogenic, implying a likely digenic/oligogenic etiology.

scholarly journals De Novo Mutation in X-Linked Hearing Loss–Associated POU3F4 in a Sporadic Case of Congenital Hearing Loss

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 169S-176S ◽  
Author(s):  
Hideaki Moteki ◽  
A. Eliot Shearer ◽  
Shuji Izumi ◽  
Yamato Kubota ◽  
Hela Azaiez ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Family History ◽  
De Novo ◽  
Massively Parallel Sequencing ◽  
Sporadic Case ◽  
De Novo Mutation ◽  
Prognostic Information ◽  
Targeted Genomic Enrichment ◽  
History Of ◽  
Auditory Skills

Objectives: In this report, we present a male patient with no family history of hearing loss, in whom we identified a novel de novo mutation in the POU3F4 gene. Methods: One hundred ninety-four (194) Japanese subjects from unrelated and nonconsanguineous families were enrolled in this study. We used targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes for identifying the genetic causes of hearing loss. Results: A novel de novo frameshift mutation of POU3F4 to c.727_728insA (p.N244KfsX26) was identified. The patient was a 7-year-old male with congenital progressive hearing loss and inner ear deformity. Although the patient had received a cochlear implant, auditory skills were still limited. The patient also exhibited developmental delays similar to those previously associated with POU3F4 mutation. Conclusion: This is the first report of a mutation in POU3F4 causing hearing loss in a Japanese patient without a family history of hearing loss. This study underscores the importance of comprehensive genetic testing of patients with hearing loss for providing accurate prognostic information and guiding the optimal management of patient rehabilitation.

scholarly journals The rare hemoglobin variant Hb Mizuho: report of a Swiss family and literature review

2021 ◽  
Author(s):  
Linet Njue ◽  
Cesare Medri ◽  
Peter Keller ◽  
Miriam Diepold ◽  
Behrouz Mansouri Taleghani ◽  
...  
Keyword(s):  
Literature Review ◽  
Hemolytic Anemia ◽  
De Novo ◽  
Clinical History ◽  
Molecular Techniques ◽  
De Novo Mutation ◽  
First Case ◽  
History Of ◽  
Transfusion Dependency ◽  
Unstable Hemoglobin

AbstractHb Mizuho is a very rare unstable hemoglobin; here, we describe the clinical history of three Swiss family members with Hb Mizuho together with a systematic review of the previously six published cases. The clinical history of the adult woman we report here is unique since this is the first Hb Mizuho presenting with Moyamoya complications and the first case reported with long-term erythrocyte exchange. The literature review showed that Hb Mizuho was mainly reported as a de novo mutation, with the exception of children descended from known cases. All published patients with this unstable hemoglobin showed severe hemolytic anemia with the exception of one; all were regularly transfused. Patients with higher HbF levels might require fewer transfusions. All patients underwent splenectomy at a median age of 4 years and had variable clinical improvement; some achieved complete resolution of transfusion dependency after splenectomy. Iron overload in Hb Mizuho patients seems to be mainly attributed to transfusions and has less to do with ineffective erythropoiesis. Diagnosis might be challenging; a normal hemoglobin electrophoresis should not rule out the diagnosis of unstable hemoglobin in patients with otherwise unexplained hemolytic anemia. This series shows the enormous utility of using molecular techniques for diagnosis.

Albumin in the Meconium of Infants with Cystic Fibrosis: A Preliminary Report

PEDIATRICS ◽  
1964 ◽  
Vol 33 (1) ◽  
pp. 115-119
Author(s):  
WILMER C. WISER ◽  
FRANCES R. BEIER
Keyword(s):  
Cystic Fibrosis ◽  
Family History ◽  
Protein Content ◽  
Preliminary Report ◽  
Diagnostic Procedure ◽  
Serum Proteins ◽  
Newborn Infants ◽  
Control Group ◽  
Abnormal Protein ◽  
History Of

Meconium samples were collected from 5 newborn infants, who had a known family history of cystic fibrosis of the pancreas but who did not present with meconium ileus, and 11 normal newborn infants. Extracts of the meconium samples were examined for the presence of serum proteins by paper and immunoelectrophoresis. Three of the infants who had a family history of cystic fibrosis of the pancreas showed protein in their meconium, and this was identified by immunoelectrophoresis as consisting mainly of albumin; each of these babies subsequently developed classic symptoms of cystic fibrosis of the pancreas. The two remaining infants had no albumin in the meconium and did not develop signs of cystic fibrosis. None of the meconium samples of the control group of infants contained detectable amounts of albumin. Possible sources of the abnormal protein content of meconium are discussed, and the suggestion that the finding of albumin in meconium of newborn infants may prove to constitute a valuable diagnostic procedure for screening newborn infants for cystic fibrosis of the pancreas is advanced.

Identification of Features Associated with Flying Phobia in Aircrew

1981 ◽  
Vol 139 (1) ◽  
pp. 38-42 ◽  
Author(s):  
R. C. B. Aitken ◽  
J. A. Lister ◽  
C. J. Main
Keyword(s):  
Family History ◽  
Skin Conductance ◽  
Predictive Value ◽  
Matched Control ◽  
Anxiety Symptoms ◽  
Control Group ◽  
Psychometric Tests ◽  
Matched Control Group ◽  
Spontaneous Fluctuation ◽  
History Of

SummaryThe psychological and physiological features of 20 aircrew consecutively referred for treatment of anxiety symptoms when flying were compared with a matched control group of uncomplaining aircrew. There were no significant differences between the two groups on psychometric tests of personality, though there were differences in skin conductance; the phobics had a higher rate of spontaneous fluctuation, and habituated less to a repeated auditory tone. More of the phobic group worried about their wives and acknowledged childhood and other adulthood phobias; more had a family history of an episode perhaps best described as flying trauma. Many were on an overseas posting when symptoms presented. These few features could correctly classify 85 per cent of the subjects into the phobic or control group. This type of ‘phobic aircrew index’ now requires to be validated prospectively for its predictive value.

scholarly journals Younger age of patients with myocardial infarction correlates with higher number of relatives with history of premature atherosclerosis

2020 ◽  
Author(s):  
Michał Ambroziak ◽  
Katarzyna Niewczas-Wieprzowska ◽  
Agnieszka Maicka ◽  
Andrzej Budaj
Keyword(s):  
Myocardial Infarction ◽  
Family History ◽  
Young Patients ◽  
Significant Risk ◽  
Control Group ◽  
Premature Coronary Artery Disease ◽  
Premature Atherosclerosis ◽  
Global Issues ◽  
Younger Age ◽  
History Of

Abstract Background. Premature coronary artery disease belongs to the most pressing global issues in a modern cardiology. Family history appears to be one of the most important and significant risk factors in young patients with myocardial infarction (MI). The aim of the study was to investigate the role of family history of premature cardiovascular disease (CVD) in patients <50 years with myocardial infarction (MI) compared to patients ≥ 50 years with MI and to young healthy people.Methods. The studied group (MI<50) consisted of 240 patients aged 26-49 years with MI. The control groups consisted of 240 patients (MI≥50) with MI aged 50-92 years and 240 healthy people aged 30-49 years.Results. There were statistically significant differences between the MI<50 and MI≥50 and young healthy groups regarding family history of premature MI/ischaemic stroke and percent of patients with of ≥2 relatives affected including parents, children, siblings, siblings of parents and grandparents (10.8%, 2.9%, 3.7%, respectively; p<0.0001). There was a statistically significant negative correlation between the age of the first episode of MI and the number of relatives with a history of premature MI/stroke (r=0.249, p<0.05) within all MI patients. Statistically significant differences between MI<50 and MI≥50 groups as well as young healthy control group were revealed regarding prevalence of smoking, body mass index (BMI), LDL, HDL, triglycerides (TG) and glucose levels.Conclusions. Younger age of patients with myocardial infarction correlates with a higher number of relatives with a history of premature MI/ischemic stroke. Thus, the family history of premature atherosclerosis involving not only the first-, but also the second-degree relatives, seems to be valuable and could be considered in an individual CVD risk evaluation in young people.

scholarly journals Study of risk factors and its correlation with constraint induced movement therapy for atherosclerosis in patients of coronary artery disease and their offspring

2020 ◽  
Vol 7 (3) ◽  
pp. 446
Author(s):  
Venugopal Margekar ◽  
Shweta Thakur ◽  
O. P. Jatav ◽  
Pankaj Yadav
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Positive Family History ◽  
Surrogate Marker ◽  
Control Group ◽  
Medical College ◽  
Constraint Induced Movement Therapy ◽  
Group Data ◽  
History Of ◽  
Artery Disease

Background: A significant percent of cardiovascular event occurs without well-known modifiable risk. A new tool for early identification for atherosclerosis is required for early intervention. Aims and objectives of the study was to study the risk factors for CAD and its correlation with CIMT.Methods: One hundred and forty subjects were studied for the risk factors of CAD in Department of Medicine of G.R. Medical College, Gwalior from 2012 to 2013. Out of 140 subjects, 100 were patients having CAD and 40 age matched subjects were included as control group. Data was also recorded from their offspring. High resolution B mode ultrasonography was performed to assess CIMT of carotid arteries. The maximum CIMT of any one side of carotid artery was taken for study.Results: CAD was more prevalent among males (78%). Majority of the offspring of cases had age between 28-42 years and majority were male (73%). Most common risk factors for CAD was dyslipidemia (48%), hypertension (24%), diabetes (12%) and smoking (21%), whereas in offspring’s of CAD patients, dyslipidemia was seen in 28%, hypertension in 3%, diabetes and tobacco smoking in 12% and 24% respectively. The CIMT of CAD patients was significantly increased with increasing the number of risk factors and the same pattern was also seen in controls.  The CIMT of asymptomatic offspring’s having positive family history was significantly more than the asymptomatic offspring without positive family history of CAD.Conclusions: CIMT measurements can be used as a surrogate marker of atherosclerosis as it has showed a direct link with number of risk factors of CAD. 

scholarly journals The Characteristics of Risk Factors in Chinese Young Women with Acute Coronary Syndrome

2020 ◽  
Author(s):  
Ruifang Liu ◽  
Fangxing Xu ◽  
Yujie Zhou ◽  
Tongku Liu
Keyword(s):  
Risk Factors ◽  
Family History ◽  
Young Women ◽  
Early Onset ◽  
Young Female ◽  
Cardiac Insufficiency ◽  
Control Group ◽  
Significant Difference ◽  
Gynecological Diseases ◽  
History Of

Abstract Background In recent years, the prevalence rate of ACS in Chinese young women has been increasing significantly, becoming the main cause of death in young female. This study aimed to investigate the characteristics and difference of risk factors in Chinese young women with ACS and to provide references for ACS prevention and treatment. Methods A 1:1 case-control study was conducted to evaluate risk factors of 415 young female patients with ACS (ACS group) who underwent PCI treatment and 415 young female cases without ACS (control group) who were hospitalized and confirmed by coronary angiography to exclude coronary heart disease from January 2010 to August 2016. The average age of the cases in the two groups was respectively (40.77±4.02) years-old and (40.57±4.01) years-old (P> 0.05). Results The risk factors in ACS group were overweight (64.10%), hypertension (49.88%), hyperlipidemia (35.66%), diabetes (23.37%), depression or anxiety disorder (16.62%), gynecological diseases (16.39%), Hyperuricemia (15.18%), family history of early onset coronary heart disease (14.94%), hyperhomocysteinemia (11.33%), hypothyroidism(14.96%), hypercholesterolemia (8.43%) and high c-reactive protein (7.47%), and were statistically significant difference (P<0.01) compared with that of control group. The average number of risk factors per case in ACS group was significantly more than that of control groups (P<0.01). There was a statistically significant difference in the number of combined risk factors of the overweight cases compared between two groups (P<0.01). Regression analysis showed that hyperlipidemia, hyperhomocysteinemia, overweight（obesity）, high CRP, hypertension, hypothyroidism, gynecological diseases, depression or anxiety, cardiac insufficiency, hypercholesterolemia, diabetes, oral contraceptives, family history of early onset CHD, and autoimmune diseases were independent risk factors (P<0.01). The bivariate correlation analysis between CRP level and age was r= -0.158 (P<0.01). This result showed the younger ACS patient is the higher serum CRP. Conclusion The independent risk factors of ACS in young women are hyperlipidemia, hyperhomocysteinemia, overweight, high CRP, hypertension, hypothyroidism, gynecological diseases, depression or anxiety, cardiac insufficiency, hypercholesterolemia, diabetes, oral contraceptives, family history of early onset CHD, and autoimmune diseases. The co-existence of multiple risk factors is the main cause suffering from ACS in young women.

scholarly journals Some Risk Factors of Chronic Functional Constipation Identified in a Pediatric Population Sample from Romania

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Claudia Olaru ◽  
Smaranda Diaconescu ◽  
Laura Trandafir ◽  
Nicoleta Gimiga ◽  
Gabriela Stefanescu ◽  
...  
Keyword(s):  
Family History ◽  
Dietary Habits ◽  
Pediatric Population ◽  
Positive Family History ◽  
Population Sample ◽  
Control Sample ◽  
Functional Constipation ◽  
Control Group ◽  
Significant Difference ◽  
History Of

We conducted an observational study over a 1-year period, including 234 children aged 4–18 years and their caregivers and a matching control group. 60.73% of the children from the study group were males. Average age for the onset of constipation was 26.39 months. The frequency of defecation was 1/4.59 days (1/1.13 days in the control group). 38.49% of the patients in the sample group had a positive family history of functional constipation. The majority of children with functional constipation come from single-parent families, are raised by relatives, or come from orphanages. Constipated subjects had their last meal of the day at later hours and consumed fast foods more frequently than the children in the control sample. We found a statistically significant difference between groups regarding obesity/overweight and constipation (χ2=104.94,  df=2,  p<0.001) and regarding physical activity and constipation (χ2=18.419;  df=3;  p<0.001). There was a positive correlation between the number of hours spent watching television/using the computer and the occurrence of the disease (F= 92.162,p<0.001, and 95% Cl). Children from broken families, with positive family history, defective dietary habits, obesity and sedentary behavior, are at higher risk to develop chronic functional constipation.

Central Centrifugal Cicatricial Alopecia: Retrospective Chart Review

2010 ◽  
Vol 14 (5) ◽  
pp. 212-222 ◽  
Author(s):  
Sejal K. Shah ◽  
Andrew F. Alexis
Keyword(s):  
Family History ◽  
Chart Review ◽  
Seborrheic Dermatitis ◽  
Positive Family History ◽  
Retrospective Chart Review ◽  
Control Group ◽  
Adult Women ◽  
History Of ◽  
Hair Care ◽  
Women Of African Descent

Background: Few studies have investigated central centrifugal cicatricial alopecia (CCCA). Thus, our understanding of CCCA is largely based on anecdotal evidence. Objective: The purpose of this study was to investigate clinical characteristics and hair care practices in CCCA patients. Methods: We conducted a single-center retrospective chart review of patients with a clinicopathologic diagnosis of CCCA. Results: Medical records of 69 patients were reviewed. Of these, 97% were female. The mean ages at onset and presentation were 38.2 and 42.4 years, respectively. All subjects for whom hair care data were available had used a traumatic practice at least once, the most common being chemical relaxer. Family history data were available for 27 subjects (39%). Of these, 56% had a positive family history of hair loss. Seborrheic dermatitis was the leading concurrent diagnosis. Limitations: Limitations include lack of a control group, retrospective design, and selection bias. Conclusions: Our results confirm that CCCA primarily affects adult women of African descent. The majority of patients presented several years after onset, suggesting that efforts to encourage earlier diagnosis are warranted. Although the role of hair care remains unclear, traumatic practices were reported in all patients in our study for whom hair care was documented.

scholarly journals Evaluation of The 10 Warning Signs In Immunodeficient Patients: Additional Suggestions

2021 ◽  
Author(s):  
Fadime Ceyda Eldeniz ◽  
Yahya Gül ◽  
Alaattin Yorulmaz ◽  
Şükrü Nail Güner ◽  
Sevgi Keles ◽  
...  
Keyword(s):  
Family History ◽  
Early Diagnosis ◽  
Chronic Diarrhea ◽  
Warning Signs ◽  
Control Group ◽  
Healthy Children ◽  
Physician Awareness ◽  
History Of ◽  
And Control ◽  
Immunological Evaluation

Abstract Objective: Ten warning signs of primary immunodeficiency (PID) were suggested by the Jeffrey Modell Foundation (JMF), to increase physician awareness of PID. These warning signs have not yet been evaluated for patients with secondary immunodeficiency (SID). This study investigated whether the 10 warning signs used for the diagnosis of PID are sufficient for the diagnosis of SID, and explored the possibility of additional signs.Methods: This prospective study was conducted between June and December 2020. The mothers of 162 patients with PID and SID, and mothers of 200 healthy children, were asked to complete a questionnaire about family and personal history in addition to the warning signs of PID developed by the JMF. A JMF score was created by giving one point for each “Yes” answer for the 10 warning signs of PID. Medical records of the patients were evaluated for possible additional warning signs for PID and SID. Results: The JMF scores of the PID (3.36 ± 1.65) and SID (3.72 ± 1.12) groups were significantly higher than the scores of the control group (0.34 ± 0.61) (p < 0.05). A sign for immunological evaluation in two patients without warning signs in the PID group was found to be chronic diarrhea. In addition to the 10 JMF warning signs, we found that consanguinity and a family history of tuberculosis were statistically significant in our PID group, compared with the SID and control groups. Conclusions: The JMF warning signs are important for early diagnosis of PID. Our study showed that these signs may also be used for the early diagnosis of SID in patients and, according to our results, in addition to the 10 JMF signs for PID, parental consanguinity, chronic diarrhea, and a family history of tuberculosis may also be considered warning signs for the early diagnosis of PID.

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