scholarly journals Exome sequencing identifies a de novo mutation of CTNNB1 gene in a patient mainly presented with retinal detachment, lens and vitreous opacities, microcephaly, and developmental delay

Medicine ◽  
2017 ◽  
Vol 96 (20) ◽  
pp. e6914 ◽  
Author(s):  
Niu Li ◽  
Yufei Xu ◽  
Guoqiang Li ◽  
Tingting Yu ◽  
Ru-en Yao ◽  
...  
Keyword(s):  
Retinal Detachment ◽  
Exome Sequencing ◽  
Developmental Delay ◽  
De Novo ◽  
De Novo Mutation ◽  
Ctnnb1 Gene ◽  
Vitreous Opacities

Sleep Exacerbations and Facial Twitching: Diagnostic Clues for ADCY5-Related Dyskinesias

2020 ◽  
Author(s):  
Margherita Nosadini ◽  
Gianluca D'Onofrio ◽  
Maria Federica Pelizza ◽  
Concetta Luisi ◽  
Davide Padrin ◽  
...  
Keyword(s):  
Movement Disorder ◽  
Developmental Delay ◽  
De Novo ◽  
Brain Magnetic Resonance Imaging ◽  
Neurological Impairment ◽  
De Novo Mutation ◽  
Oligoclonal Bands ◽  
Emotional Stimuli ◽  
Childhood Onset ◽  
Ataxic Gait

Abstract Background Mutations in the adenylate cyclase 5 (ADCY5) gene are associated with childhood-onset paroxysmal dyskinesia. Methods We report a new video-documented case of pediatric ADCY5-related dyskinesia with de novo ADCY5 mutation. Results A boy born to nonconsanguineous parents after an uneventful pregnancy had developmental delay and hypotonia. At the age of 7 months, he presented with paroxysmal jerky–choreic–dystonic involuntary movements in wakefulness involving limbs, trunk, and face, exacerbated by emotional stimuli. These episodes gradually worsened in duration and frequency: at the age of 2.5 years, they occurred up to six times per day, and appeared also during sleep in prolonged bouts; the boy also had basal choreoathetoid–dystonic movements, hyperactivity, paraparetic–ataxic gait, generalized hypotonia with brisk tendon reflexes, drooling, and language delay with intellectual disability. Brain magnetic resonance imaging, electroencephalogram, electromyogram, eye review, metabolic investigations, oligoclonal bands, and autoantibodies were normal. Extensive genetic testing had not let to a diagnosis, until a heterozygous de novo mutation c.1252C > T (p.Arg418Trp) was identified in the ADCY5 gene. Clonazepam had partial effectiveness. The boy walked at the age of 3.5 years. At the age of 5 years, the paroxysmal movement disorder has slightly improved. Conclusion ADCY5 mutations should be considered among the differential diagnoses of early-onset paroxysmal choreic–athetosic–myoclonic–dystonic movement disorder involving limbs, trunk, and face, in patients with global neurological impairment with hypotonia and developmental delay. Facial dyskinesias and exacerbation by drowsiness/sleep and emotional stimuli are important clues that may allow a timely recognition of the disorder and avoidance of unnecessary diagnostic investigations.

A de novo mutation affecting human TrkB associated with severe obesity and developmental delay

2004 ◽  
Vol 7 (11) ◽  
pp. 1187-1189 ◽  
Author(s):  
Giles S H Yeo ◽  
Chiao-Chien Connie Hung ◽  
Justin Rochford ◽  
Julia Keogh ◽  
Juliette Gray ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Severe Obesity ◽  
De Novo ◽  
De Novo Mutation

scholarly journals Case Report: A Novel De Novo Missense Mutation of the GRIA2 Gene in a Chinese Case of Neurodevelopmental Disorder With Language Impairment

2021 ◽  
Vol 12 ◽  
Author(s):  
Bingbo Zhou ◽  
Chuan Zhang ◽  
Lei Zheng ◽  
Zhiqiang Wang ◽  
Xue Chen ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Missense Mutation ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
Language Impairment ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Behavioral Abnormalities ◽  
Whole Exome ◽  
Chinese Case

Introduction: Neurodevelopmental disorders with language impairment and behavioral abnormalities (NEDLIB) are a disease caused by heterozygous variants in the glutamate ionotropic receptor AMPA type subunit 2 (GRIA2) gene, which manifest as impaired mental development or developmental delay, behavioral abnormalities including autistic characteristics, and language disorders. Currently, only a few mutations in the GRIA2 gene have been discovered.Methods: A GRIA2 variation was detected in a patient by whole-exome sequencing, and the site was validated by Sanger sequencing from the family.Results: We report a Chinese case of NEDLIB in a girl with language impairment and developmental delay through whole-exome sequencing (WES). Genetic analysis showed that there was a de novo missense mutation, c.1934T > G (p.Leu645Arg), in the GRIA2 gene (NM_001083619.1), which has never been reported before.Conclusion: Our case shows the potential diagnostic role of WES in NEDLIB, expands the GRIA2 gene mutation spectrum, and further deepens the understanding of NEDLIB. Deepening the study of the genetic and clinical heterogeneity, treatment, and prognosis of the disease is still our future challenge and focus.

scholarly journals Case Report: A Novel de novo Mutation in DNM1L Presenting With Developmental Delay, Ataxia, and Peripheral Neuropathy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yanping Wei ◽  
Min Qian
Keyword(s):  
Peripheral Neuropathy ◽  
Developmental Delay ◽  
De Novo ◽  
Refractory Epilepsy ◽  
De Novo Mutation ◽  
Global Developmental Delay ◽  
Missense Mutations ◽  
Related Protein ◽  
Resonance Imaging ◽  
Genetic Results

DNM1L encodes dynamin-related protein 1 (Drp1), which is a member of the dynamin superfamily of GTPases and mediates mitochondrial and peroxisomal fission. In humans, several de novo heterozygous missense mutations in DNM1L have been reported, which were characterized by devastating courses with refractory epilepsy, myoclonus, and brain atrophy on MRI. We describe a 4.5-year-old male child harboring a novel de novo mutation in DNM1L presenting a phenotype of developmental delay, ataxia, and peripheral neuropathy. The clinical features, magnetic resonance imaging findings, and genetic results were summarized. Meanwhile, all the cases of DNM1L mutations reported were reviewed. DNM1L variants may need to be considered in phenotypes that include global developmental delay, peripheral neuropathy, and ataxia.

Whole Exome Analysis of Relapsing Patients with Acute Promyelocytic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2892-2892 ◽  
Author(s):  
Cecile Bally ◽  
Jacqueline Lehmann-Che ◽  
Bruno Cassinat ◽  
Lionel Ades ◽  
Eric Letouze ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Research Funding ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Mapk Signaling ◽  
Copy Number Variations ◽  
Leukemic Cells ◽  
De Novo Mutation ◽  
Whole Exome

Abstract Background : APL is, in the vast majority of cases, driven by t(15 ;17) translocation, which leads to PML/RARA rearrangement. Remarkably, APL is an uncommon genetically simple disease and only few additional alterations, cooperating with PML/RAR, have been described at diagnostic (Welch et al, Cell 2012). Most APL can be cured with targeted therapy combining all-trans retinoic acid (ATRA) and chemotherapy (CT). However, genetic mechanisms underlying the 10-15% relapses observed with this regimen remain unclear. The goal of the present study was to identify mutations that cooperate with PML/RAR and those responsible for acquired resistance to ATRA-CT treatment in APL patients by whole-exome sequencing of diagnostic/ remission/relapse trios. Methods: Newly diagnosed APL patients included in clinical trials of the French Swiss Belgian APL group between 1994 and 2008, treated with ATRA-CT, before the introduction of first-line ATO, who experienced at least one relapse and had adequate material, were studied. We collected retrospectively 64 samples from 23 patients, including 23 diagnostic samples, 18 at first complete remission (CR) and 23 at relapse (22 first relapse and 1 second relapse). Whole exome-sequencing was performed on all samples. DNA libraries were prepared with the SureSelect human v5 kit (Agilent) and sequenced on Hiseq1000 (Illumina). The bioinformatic analysis was performed by GECO/integragen using CASAVA variant calling (Illumina) and dedicated pipeline. 18 trios and 5 duos passed the stringent quality control and were analyzed for somatic variants and copy number variations (CNV). Results : After elimination of polymorphisms, the median number of somatic variants corresponding to de novo mutation at diagnosis was 14, while only 3 new somatic variants appeared at relapse (figure 1). Notably, we failed to detect oncogene alterations other than PML/RARA in 7/23 (30%) patients. At diagnostic, 39% of patients (9/23) presented the common FLT3 alterations and at relapse 22% (5/23) of patients presented the known RARA mutations. Moreover, recurrent alterations were observed in activators of the MAPK signaling (22%): NRAS (2 patients), BRAF (1 patient), KRAS (1 patient), SPRY1 (1 patient). Mutations in the NT5C2 gene (3 patients), coding a 5'nucleotidase implicated in resistance to nucleoside-analog therapy, were solely observed at relapse, as in acute lymphoblastic leukemia (ALL). Abnormalities of epigenetic regulators were also detected at diagnostic and/or relapse: WT1 (7 patients, 30%), NSD1 (2 patients), TET2 (1 patient), ASXL1 (1 patient) and MED12 (2 patients). Homozygote WT1 inactivation by mutation plus neutral copy LOH occurred in 3 patients at relapse. The genetic markers identified allowed us to construct several evolution models. In 8 patients (35%), the diagnostic and relapse clones were clearly distinct, supporting the fact that they independently derived from pre-leukemic cells that survived ATRA/chemotherapy. In contrast, other relapses appeared to derive from the diagnostic clone. Conclusion: Our data highlight the genetic simplicity of APL with very few alterations detected and 30% patients without identified mutations in addition to PML/RARa. Our results support the existence of two prototypic mechanisms of relapse: re-emergence of a new APL from persisting pre-leukemic cells and relapse from APLs often expressing strong oncogenes at diagnosis, impeding therapy response and favoring the acquisition of resistance mutations at relapse, including PML/RARA or NT5C2. It will be interesting to assess the prevalence of those two mechanisms in the exceptional cases of relapse in patients treated with more recent frontline regimens that combine ATRA and arsenic in APL. Disclosures Ades: Celgene, Takeda, Novartis, Astex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fenaux:Celgene, Janssen,Novartis, Astex, Teva: Honoraria, Research Funding.

scholarly journals Erratum: Exome sequencing identifies a de novo mutation in HDAC8 associated with Cornelia de Lange syndrome

2015 ◽  
Vol 60 (3) ◽  
pp. 165-165 ◽  
Author(s):  
Lei Feng ◽  
Daizhan Zhou ◽  
Zhou Zhang ◽  
Yun Liu ◽  
Yabo Yang
Keyword(s):  
Exome Sequencing ◽  
De Novo ◽  
De Novo Mutation ◽  
Cornelia De Lange Syndrome ◽  
Cornelia De Lange

scholarly journals Whole-exome sequencing identifies de novo mutation in the COL1A1 gene to underlie the severe osteogenesis imperfecta

2015 ◽  
Vol 9 (1) ◽  
Author(s):  
Katre Maasalu ◽  
Tiit Nikopensius ◽  
Sulev Kõks ◽  
Margit Nõukas ◽  
Mart Kals ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
De Novo Mutation ◽  
Col1a1 Gene ◽  
Whole Exome

scholarly journals A de novo frameshift variant of ANKRD11 (c.1366_1367dup) in a Chinese patient with KBG syndrome

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing Chen ◽  
Zhongmin Xia ◽  
Yulin Zhou ◽  
Xiaomin Ma ◽  
Xudong Wang ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
Slow Wave ◽  
In Silico ◽  
De Novo ◽  
Triangular Face ◽  
Whole Exome ◽  
Kbg Syndrome

Abstract Background KBG syndrome is a rare autosomal dominant genetic disease mainly caused by pathogenic variants of ankyrin repeat domain-containing protein 11 (ANKRD11) or deletions involving ANKRD11. Herein, we report a novel de novo heterozygous frameshift ANKRD11 variant via whole exome sequencing in a Chinese girl with KBG syndrome. Case presentation A 2-year-2-month-old girl presented with a short stature and developmental delay. Comprehensive physical examinations, endocrine laboratory tests and imaging examination were performed. Whole‐exome sequencing and Sanger sequencing were used to detect and confirm the variant associated with KBG in this patient, respectively. The pathogenicity of the variant was further predicted by several in silico prediction tools. The patient was diagnosed as KBG syndrome with a short stature and developmental delay, as well as characteristic craniofacial abnormalities, including a triangular face, long philtrum, wide eyebrows, a broad nasal bridge, prominent and protruding ears, macrodontia of the upper central incisors, dental crowding, and binocular refractive error. Her skeletal anomalies included brachydactyly, fifth finger clinodactyly, and left-skewed caudal vertebrae. Electroencephalographic results generally showed normal background activity with sporadic spikes and slow wave complexes, as well as multiple spikes and slow wave complexes in the bilateral parietal, occipital, and posterior temporal regions during non-rapid-eye-movement sleep. Brain MRI showed a distended change in the bilateral ventricles and third ventricle, as well as malformation of the sixth ventricle. Whole exome sequencing revealed a novel heterozygous frameshift variant in the patient, ANKRD11 c.1366_1367dup, which was predicted to be pathogenic through in silico analysis. The patient had received physical therapy since 4 months of age, and improvement of gross motor dysfunction was evident. Conclusions The results of this study expand the spectrum of ANKRD11 variants in KBG patients and provide clinical phenotypic data for KBG syndrome at an early age. Our study also demonstrates that whole exome sequencing is an effective method for the diagnosis of rare genetic disorders.

Sign in / Sign up

Export Citation Format

Share Document