scholarly journals Case Report: First Occurrence of Plasmablastic Lymphoma in Activated Phosphoinositide 3-Kinase δ Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Zexi Yin ◽  
Xin Tian ◽  
Runying Zou ◽  
Xiangling He ◽  
Keke Chen ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Respiratory Infections ◽  
Plasmablastic Lymphoma ◽  
Heterozygous Mutation ◽  
Recurrent Respiratory Infections ◽  
Whole Exome ◽  
First Occurrence ◽  
Phosphoinositide 3 Kinase ◽  
Secondary Tumours

Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal dominant primary immunodeficiency caused by acquired gene function mutation (GOF). APDS has a variety of clinical phenotypes, particularly recurrent respiratory infections and lymphoproliferation. Here we report a pediatric patient with APDS who presented with recurrent respiratory infections, lymphoproliferation, hepatosplenomegaly, bronchoscopy suggesting numerous nodular protrusions in the airways and a decrease in both T and B lymphocytes, and progression to plasmablastic lymphoma (PBL) after 1 year. Whole exome sequencing revealed a heterozygous mutation in the PIK3CD gene (c.3061 G>A p.E1021K). This is the first reported case of APDS combined with PBL and pediatricians should follow up patients with APDS regularly to be alert for secondary tumours.

scholarly journals A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy

2021 ◽  
Author(s):  
Qing Li ◽  
Chengfeng Wang ◽  
Wei Li ◽  
Zaiqiang Zhang ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Skin Biopsy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Collagen Type Iv ◽  
Lacunar Infarcts ◽  
Whole Exome

AbstractPontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

Postcricoid Hemangioma of Childhood: Report of Four Cases

2006 ◽  
Vol 115 (3) ◽  
pp. 191-194 ◽  
Author(s):  
Ramez J. Awwad ◽  
Anthony J. Mortelliti
Keyword(s):  
General Anesthesia ◽  
Incidental Findings ◽  
Respiratory Infections ◽  
Neck Region ◽  
Vocal Folds ◽  
Head And Neck Region ◽  
True Incidence ◽  
Flexible Laryngoscopy ◽  
Recurrent Respiratory Infections

Hemangiomas are the most common tumor of infancy, and the vast majority occur in the head and neck region. In children, laryngeal hemangiomas typically occur below the level of the true vocal folds, in the region of the subglottis, and other sites are exceedingly rare. We present four cases of hemangiomas located in the postcricoid region of the hypopharynx. Because of the location of these lesions, children may present with obstructive symptoms such as dysphagia, intermittent aspiration, hypersalivation, or recurrent respiratory infections. Clinical diagnosis is relatively easily made with flexible laryngoscopy, as the lesions have a propensity to enlarge with crying or straining. When these patients are examined under general anesthesia in a relaxed state, however, the lesions are typically much smaller, and can even go unnoticed. Unlike other reported cases, the postcricoid hemangiomas in our patients were not causing any symptoms and were simply incidental findings. Thus, we believe that the true incidence of postcricoid hemangiomas is likely higher than reports suggest. To our knowledge, we report the longest follow-up (6 years) of a patient with a postcricoid hemangioma and are the first to describe the natural course of such a lesion.

scholarly journals Effectiveness and safety of pidotimod in recurrent respiratory infections in children: a pilot study

2019 ◽  
Vol 6 (5) ◽  
pp. 2012 ◽  
Author(s):  
T. C. Acharya ◽  
Kundan Nivangune ◽  
Snehal Muchhala ◽  
Rishi Jain
Keyword(s):  
Prospective Observational Study ◽  
Standard Treatment ◽  
Respiratory Infections ◽  
Single Centre ◽  
The Past ◽  
Recurrent Respiratory Infections ◽  
Before And After ◽  
Antibiotic Courses

Background: Recurrent respiratory infections (RRIs) are common in children especially in age 1 to 6 years. Pidotimod, an immunostimulant has been found to lower the recurrences of RRIs and improve the quality of life. The Objective of this study was to assess the efficacy and safety of pidotimod in children with recurrent respiratory infections (RRIs).Methods: In this single-centre, prospective, observational study, children aged 2 to 15 years diagnosed with RRIs were included. RRIs were defined as occurrence of 3 or more episodes of acute respiratory infections (ARIs) or more than 15 days of respiratory symptoms in the past 3 months. These children were treated with pidotimod in addition to standard care treatment. Treatment duration was two months and the follow-up continued for three months. Number of RRIs and severity of RRIs, antibiotic courses and rate of hospitalization before and after treatment were compared.Results: In total 25 children included in the study, mean age was 7.34±3.63 years. Among them, 68% were males. After treatment with pidotimod, there was significant reduction in mean number of ARI episodes (3.84±0.85 at baseline to 0.48±0.51 at follow-up, p<0.0001). Also, there was significant reduction in the duration of acute infectious episodes (p<0.0001), need of antibiotic courses (p<0.0001) and rates of hospitalization (p<0.0001). No safety concerns were identified and pidotimod was well tolerated.Conclusions: Addition of pidotimod to the standard treatment in children with RRIs significantly reduces the recurrence, duration of repeat infectious episodes, need of antibiotic treatments and future rates of hospitalizations. These findings support previous data.

scholarly journals A Novel CRYBB2 Stopgain Mutation Causing Congenital Autosomal Dominant Cataract in a Chinese Family

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yu Zhou ◽  
Yaru Zhai ◽  
Lulin Huang ◽  
Bo Gong ◽  
Jie Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Congenital Cataract ◽  
Autosomal Dominant ◽  
Family Members ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Whole Exome ◽  
Causal Mutation ◽  
Control Samples

Congenital cataract is the most common cause of the visual disability and blindness in childhood. This study aimed to identify gene mutations responsible for autosomal dominant congenital cataract (ADCC) in a Chinese family using next-generation sequencing technology. This family included eight unaffected and five affected individuals. After complete ophthalmic examinations, the blood samples of the proband and two available family members were collected. Then the whole exome sequencing was performed on the proband and Sanger sequencing was applied to validate the causal mutation in the two family members and control samples. After the whole exome sequencing data were filtered through a series of existing variation databases, a heterozygous mutation c.499T<G (p.E167X) in CRYBB2 gene was found. And the results showed that the mutation cosegregated with the disease phenotype in the family and was absolutely absent in 1000 ethnicity-matched control samples. Thus, the heterozygous mutation c.499T<G (p.E167X) in CRYBB2 was the causal mutation responsible for this ADCC family. In conclusion, our findings revealed a novel stopgain mutation c.499T<G (p.E167X) in the exon 6 of CRYBB2 which expanded the mutation spectrum of CRYBB2 in Chinese congenital cataract population and illustrated the important role of CRYBB2 in the genetics research of congenital cataract.

scholarly journals Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1277
Author(s):  
Roxane Van Heurck ◽  
Maria Teresa Carminho-Rodrigues ◽  
Emmanuelle Ranza ◽  
Caterina Stafuzza ◽  
Lina Quteineh ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Autosomal Dominant ◽  
Diagnostic Yield ◽  
Autosomal Recessive Inheritance ◽  
Nonsyndromic Hearing Loss ◽  
Whole Exome ◽  
Syndromic Hearing Loss ◽  
Children With Hearing Loss

Purpose: Hearing loss is characterized by an extensive genetic heterogeneity and remains a common disorder in children. Molecular diagnosis is of particular benefit in children, and permits the early identification of clinically-unrecognized hearing loss syndromes, which permits effective clinical management and follow-up, including genetic counselling. Methods: We performed whole-exome sequencing with the analysis of a panel of 189 genes associated with hearing loss in a prospective cohort of 61 children and 9 adults presenting mainly with isolated hearing loss. Results: The overall diagnostic rate using exome sequencing was 47.2% (52.5% in children; 22% in adults). In children with confirmed molecular results, 17/32 (53.2%) showed autosomal recessive inheritance patterns, 14/32 (43.75%) showed an autosomal dominant condition, and one case had X-linked hearing loss. In adults, the two patients showed an autosomal dominant inheritance pattern. Among the 32 children, 17 (53.1%) had nonsyndromic hearing loss and 15 (46.7%) had syndromic hearing loss. One adult was diagnosed with syndromic hearing loss and one with nonsyndromic hearing loss. The most common causative genes were STRC (5 cases), GJB2 (3 cases), COL11A1 (3 cases), and ACTG1 (3 cases). Conclusions: Exome sequencing has a high diagnostic yield in children with hearing loss and can reveal a syndromic hearing loss form before other organs/systems become involved, allowing the surveillance of unrecognized present and/or future complications associated with these syndromes.

A new case of autosomal dominant small vessel disease carrying a novel heterozygous mutation in HTRA1 gene: 2-year follow-up

2018 ◽  
Vol 39 (8) ◽  
pp. 1479-1481 ◽  
Author(s):  
A. R. Pati ◽  
C. Battisti ◽  
I. Taglia ◽  
P. Galluzzi ◽  
M. Bianchi ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Heterozygous Mutation ◽  
Vessel Disease

scholarly journals Common Variable Immunodeficiency with Genetic Defects Identified by Whole Exome Sequencing

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Ran Li ◽  
Yali Zheng ◽  
Yuqian Li ◽  
Rongbao Zhang ◽  
Fang Wang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Common Variable Immunodeficiency ◽  
Respiratory Infections ◽  
Genetic Diagnosis ◽  
Genetic Defects ◽  
Compound Heterozygous ◽  
Recurrent Respiratory Infections ◽  
Whole Exome ◽  
Common Variable

Common variable immunodeficiency (CVID) belongs to the primary immunodeficiency disorders (PIDs), presenting a profound heterogeneity in phenotype and genotype, with monogenic or complex causes. Recurrent respiratory infections are the most common clinical manifestations. CVID patients can also develop various autoimmune and lymphoproliferative complications. Genetic testing such as whole exome sequencing (WES) can be utilized to investigate likely genetic defects, helping for better clinical management. We described the clinical phenotypes of three sporadic cases of CVID, who developed recurrent respiratory infections with different autoimmune and lymphoproliferative complications. WES was applied to screen disease-causing or disease-associated mutations. Two patients were identified to have monogenic disorders, with compound heterozygous mutations in LRBA for one patient and a frameshift insertion in NFKB1 for another. The third patient was identified to be a complex form of CVID. Two novel mutations were identified, respectively, in LRBA and NFKB1. A combination of clinical and genetic diagnosis can be more extensively utilized in the clinical practice due to the complexity and heterogeneity of CVID.

scholarly journals Tomographic Study of the Malformation Complex in Correlation With the Genotype in Patients With Robinow Syndrome: Review Article

2020 ◽  
Vol 8 ◽  
pp. 232470962091177
Author(s):  
Ali Al Kaissi ◽  
Vladimir Kenis ◽  
Mohammad Shboul ◽  
Franz Grill ◽  
Rudolf Ganger ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Respiratory Infections ◽  
Three Dimensional ◽  
Fine Motor ◽  
Heterozygous Mutation ◽  
Number Of Children ◽  
Clinical Presentations ◽  
Robinow Syndrome ◽  
Chromosome 9Q22

We aimed to understand the etiology behind the abnormal craniofacial contour and other clinical presentations in a number of children with Robinow syndrome. Seven children with Robinow syndrome were enrolled in this study (autosomal recessive caused by homozygous mutations in the ROR2 gene on chromosome 9q22, and the autosomal dominant caused by heterozygous mutation in the WNT5A gene on chromosome 3p14). In the autosomal recessive (AR) group, the main clinical presentations were intellectual, disability, poor schooling achievement, episodes of headache/migraine, and poor fine motor coordinative skills, in addition to massive restrictions of the spine biomechanics causing effectively the development of kyposcoliosis and frequent bouts of respiratory infections. Three-dimensional reconstruction computed tomography scan revealed early closure of the metopic and the squamosal sutures of skull bones. Massive spinal malsegmentation and unsegmented spinal bar were noted in the AR group. In addition to severe mesomelia and camptodactyly, in the autosomal dominant (AD) group, no craniosynostosis but few Wormian bones and the spine showed limited malsegemetation, and no mesomelia or camptodactyly have been noted. We wish to stress that little information is available in the literature regarding the exact pathology of the cranial bones, axial, and appendicular malformations in correlation with the variable clinical presentations in patients with the 2 types of Robinow syndrome.

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