scholarly journals Phenotypic expansion in DDX3X – a common cause of intellectual disability in females

2018 ◽  
Author(s):  
Xia Wang ◽  
Jill A. Rosenfeld ◽  
Carlos A. Bacino ◽  
Fernando Scaglia ◽  
LaDonna Immken ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Congenital Heart ◽  
De Novo ◽  
Late Onset ◽  
Common Cause ◽  
Respiratory Problems ◽  
Clinical Presentations ◽  
Mitochondrial Dna Depletion ◽  
Common Causes ◽  
Dna Variants

AbstractDe novo variants in DDX3X account for 1-3% of unexplained intellectual disability (ID), one of the most common causes of ID, in females. Forty-seven patients (44 females, 3 males) have been described. We identified 29 additional individuals carrying 27 unique DDX3X variants in the setting of complex clinical presentations including developmental delay or ID. In addition to previously reported manifestations, rare or novel phenotypes were identified including respiratory problems, congenital heart disease, skeletal muscle mitochondrial DNA depletion, and late-onset neurologic decline. Our findings expand the spectrum of DNA variants and phenotypes associated with DDX3X disorders.

A de novo 1q22q23.1 Interstitial Microdeletion in a Girl with Intellectual Disability and Multiple Congenital Anomalies Including Congenital Heart Defect

2018 ◽  
Vol 154 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Beata Aleksiūnienė ◽  
Egle Preiksaitiene ◽  
Aušra Morkūnienė ◽  
Laima Ambrozaitytė ◽  
Algirdas Utkus
Keyword(s):  
Intellectual Disability ◽  
Congenital Heart Defect ◽  
Congenital Heart ◽  
De Novo ◽  
Molecular Karyotyping ◽  
Pcr Analysis ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Protein Coding ◽  
Heart Defect

Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23.1 region, arr[GRCh37] 1q22q23.1(155630752_157193893)×1. Real-time PCR analysis confirmed its de novo origin. The deleted region encompasses 50 protein-coding genes, including the morbid genes APOA1BP, ARHGEF2, LAMTOR2, LMNA, NTRK1, PRCC, RIT1, SEMA4A, and YY1AP1. Although the unique phenotype observed in our patient can arise from the haploinsufficiency of the dosage-sensitive LMNA gene, the dosage imbalance of other genes implicated in the rearrangement could also contribute to the phenotype. Further studies are required for the delineation of the phenotype associated with this rare chromosomal alteration and elucidation of the critical genes for manifestation of the specific clinical features.

scholarly journals Reported symptoms differentiate diagnoses in children with exercise-induced respiratory problems: findings from the Swiss Paediatric Airway Cohort (SPAC)

2020 ◽  
Author(s):  
Eva SL Pedersen ◽  
Carmen CM de Jong ◽  
Cristina Ardura-Garcia ◽  
Maria Christina Mallet ◽  
Juerg Barben ◽  
...  
Keyword(s):  
Late Onset ◽  
Outpatient Clinics ◽  
Relative Risk Ratio ◽  
List Type ◽  
Multinomial Regression ◽  
Management Guidelines ◽  
Respiratory Problems ◽  
Clinical Presentations ◽  
Dysfunctional Breathing ◽  
Exercise Induced

AbstractBackgroundExercise-induced breathing problems with similar clinical presentations can have different aetiologies. This makes distinguishing common diagnoses such as asthma, extrathoracic and thoracic dysfunctional breathing (DB), insufficient fitness, and chronic cough difficult.ObjectiveWe studied which parent-reported, exercise-induced symptoms (EIS) can help distinguish diagnoses of EIS in children seen in respiratory outpatient clinics.MethodsThis study was nested in the Swiss Paediatric Airway Cohort (SPAC), an observational study of children aged 0-17 years referred to paediatric respiratory outpatient clinics in Switzerland. We studied children aged 6-17 years and compared information on EIS from parent-completed questionnaires between children with different diagnoses. We used multinomial regression to analyse whether parent-reported symptoms differed between diagnoses (asthma as base).ResultsAmong 1109 children, EIS were reported for 732 (66%) (mean age 11 years, 318 of 732 [43%] female). Among the symptoms, dyspnoea best distinguished thoracic DB (relative risk ratio [RRR] 5.4, 95%CI 1.3-22) from asthma. Among exercise triggers, swimming best distinguished thoracic DB (RRR 2.4, 95%CI 1.3-6.2) and asthma plus DB (RRR 1.8, 95%CI 0.9-3.4) from asthma only. Late onset of EIS was less common for extrathoracic DB (RRR 0.1, 95%CI 0.03-0.5) and thoracic DB (RRR 0.4, 95%CI 0.1-1.2) compared with asthma. Localisation of dyspnoea (throat vs. chest) differed between extrathoracic DB (RRR 2.3, 95%CI 0.9-5.8) and asthma. Reported respiration phase (inspiration or expiration) did not help distinguish diagnoses.ConclusionParent-reported symptoms help distinguish different diagnoses in children with EIS. This highlights the importance of physicians obtaining detailed patient histories.Highlights boxWhat is already known about this topic?Experts suggest that information about the symptoms and their onset and duration can assist accurate diagnosis of children with exercise-induced respiratory problems, but no original studies have tested this. (29/35 words)What does this article add to our knowledge?Exercise-induced symptoms reported by parents and further information about their onset, triggers, and effects of treatment help differentiate diagnoses in children with exercise-induced respiratory problems. (25/35 words)How does this study impact current management guidelines?Our results emphasize the importance of taking detailed symptom histories of children with exercise-induced problems, and suggest which questions are most helpful.

Persistent Hyperplastic Primary Vitreous with Microphthalmia and Coloboma in a Patient with Okur-Chung Neurodevelopmental Syndrome

2021 ◽  
pp. 1-5
Author(s):  
Hiroaki Murakami ◽  
Tomoko Uehara ◽  
Yumi Enomoto ◽  
Naoto Nishimura ◽  
Tatsuro Kumaki ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Autosomal Dominant ◽  
De Novo ◽  
Autosomal Dominant Disorder ◽  
Immune Systems ◽  
Ocular Manifestations ◽  
Pathogenic Variants ◽  
Persistent Hyperplastic Primary Vitreous ◽  
Clinical Presentations ◽  
The Brain

Okur-Chung neurodevelopmental syndrome is a rare autosomal dominant disorder caused by pathogenic variants in <i>CSNK2A1</i>, which encodes the alpha 1 catalytic subunit of ­casein kinase II. This syndrome is characterized by intellectual disability, developmental delay, and multisystemic ­abnormalities including those of the brain, extremities, and skin as well as cardiovascular, gastrointestinal, and immune systems. In this study, we describe a 5-year-old boy with a de novo novel nonsense variant in <i>CSNK2A1</i>, NM_001895.3:c.319C&#x3e;T (p.Arg107*). He showed bilateral persistent hyperplastic primary vitreous with microphthalmia, lens dysplasia, and coloboma. Ocular manifestations are very rare in this syndrome, and this study expands the spectrum of the clinical presentations of this syndrome.

scholarly journals De novo missense variants in PPP1CB are associated with intellectual disability and congenital heart disease

2016 ◽  
Vol 135 (12) ◽  
pp. 1399-1409 ◽  
Author(s):  
Lijiang Ma ◽  
Yavuz Bayram ◽  
Heather M. McLaughlin ◽  
Megan T. Cho ◽  
Alyson Krokosky ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Intellectual Disability ◽  
Congenital Heart ◽  
De Novo ◽  
Missense Variants

scholarly journals Case report: adult onset diabetes with partial pancreatic agenesis and congenital heart disease due to a de novo GATA6 mutation

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Begona Sanchez-Lechuga ◽  
Muhammad Saqlain ◽  
Nicholas Ng ◽  
Kevin Colclough ◽  
Conor Woods ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Case Report ◽  
Congenital Heart ◽  
De Novo ◽  
Adult Onset ◽  
Onset Diabetes ◽  
Adult Onset Diabetes ◽  
Pancreatic Agenesis

scholarly journals A novel de novo DDX3X missense variant in a female with brachycephaly and intellectual disability: a case report

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Giada Moresco ◽  
Jole Costanza ◽  
Carlo Santaniello ◽  
Ornella Rondinone ◽  
Federico Grilli ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Clinical Presentation ◽  
De Novo ◽  
Clinical Signs ◽  
Missense Variant ◽  
Psychomotor Development ◽  
Helicase Domain ◽  
Protein Activity ◽  
Mrna Metabolism ◽  
Pathogenic Variants

Abstract Background De novo pathogenic variants in the DDX3X gene are reported to account for 1–3% of unexplained intellectual disability (ID) in females, leading to the rare disease known as DDX3X syndrome (MRXSSB, OMIM #300958). Besides ID, these patients manifest a variable clinical presentation, which includes neurological and behavioral defects, and abnormal brain MRIs. Case presentation We report a 10-year-old girl affected by delayed psychomotor development, delayed myelination, and polymicrogyria (PMG). We identified a novel de novo missense mutation in the DDX3X gene (c.625C > G) by whole exome sequencing (WES). The DDX3X gene encodes a DEAD-box ATP-dependent RNA-helicase broadly implicated in gene expression through regulation of mRNA metabolism. The identified mutation is located just upstream the helicase domain and is suggested to impair the protein activity, thus resulting in the altered translation of DDX3X-dependent mRNAs. The proband, presenting with the typical PMG phenotype related to the syndrome, does not show other clinical signs frequently reported in presence of missense DDX3X mutations that are associated with a most severe clinical presentation. In addition, she has brachycephaly, never described in female DDX3X patients, and macroglossia, that has never been associated with the syndrome. Conclusions This case expands the knowledge of DDX3X pathogenic variants and the associated DDX3X syndrome phenotypic spectrum.

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