CHARGE syndrome patient with novel CHD7 mutation presenting with severe laryngomalacia and feeding difficulty

2020 ◽  
Vol 13 (7) ◽  
pp. e233037
Author(s):  
Cheuk Lam Lau ◽  
Yuet Yee Chee ◽  
Brian Hon Yin Chung ◽  
Ming Sum Rosanna Wong
Keyword(s):  
Diagnostic Criteria ◽  
Novel Mutation ◽  
Choanal Atresia ◽  
Charge Syndrome ◽  
Clinical Genetics ◽  
Chd7 Gene ◽  
Swallowing Difficulties ◽  
Major Criterion ◽  
Atypical Phenotype ◽  
Chd7 Mutation

We report a case of CHARGE syndrome with atypical phenotype and a novel mutation in the CHD7 gene. Laryngomalacia and swallowing difficulties are prominent features in this case. These are commonly found in patients with CHARGE syndrome and are well described in previous studies. However, with the traditional diagnostic criteria, diagnosis is difficult without the presence of coloboma or choanal atresia. Early diagnosis is possible with the aid of clinical genetics. The current diagnostic criteria would need to be broadened with the inclusion of pathogenic CHD7 variant status as a major criterion. Further research on the function of CHD7 gene may also give us more insight on the pathogenic mechanism of various clinical features of CHARGE syndrome.

scholarly journals De Novo Duplication in the CHD7 Gene Associated With Severe CHARGE Syndrome

2019 ◽  
Vol 12 ◽  
pp. 117863101983901 ◽  
Author(s):  
Laura Pranckėnienė ◽  
Eglė Preikšaitienė ◽  
Lucie Gueneau ◽  
Alexandre Reymond ◽  
Vaidutis Kučinskas
Keyword(s):  
Umbilical Hernia ◽  
Developmental Disorder ◽  
Autosomal Dominant ◽  
De Novo ◽  
Choanal Atresia ◽  
Sensory System ◽  
Charge Syndrome ◽  
Linea Alba ◽  
Congenital Hernia ◽  
Chd7 Gene

CHARGE syndrome is an autosomal dominant developmental disorder associated with a constellation of traits involving almost every organ and sensory system, in particular congenital anomalies, including choanal atresia and malformations of the heart, inner ear, and retina. Variants in CHD7 have been shown to cause CHARGE syndrome. Here, we report the identification of a novel de novo p.Asp2119_Pro2120ins6 duplication variant in a conserved region of CHD7 in a severely affected boy presenting with 3 and 5 of the CHARGE cardinal major and minor signs, respectively, combined with congenital umbilical hernia, congenital hernia at the linea alba, mildly hypoplastic inferior vermis, slight dilatation of the lateral ventricles, prominent metopic ridge, and hypoglycemic episodes.

scholarly journals Three Novel Mutations of CHD7 Gene in Two Turkish Patients with Charge Syndrome; A Double Point Mutation and an Insertion

2015 ◽  
Vol 18 (1) ◽  
pp. 65-70
Author(s):  
Ozlem Giray Bozkaya ◽  
E. Ataman ◽  
C. Randa ◽  
D. Onur Cura ◽  
S. Gürsoy ◽  
...  
Keyword(s):  
Genetic Disease ◽  
Double Point ◽  
Heart Defects ◽  
Choanal Atresia ◽  
Charge Syndrome ◽  
Dna Binding Protein ◽  
The Other ◽  
Novel Mutations ◽  
Chd7 Gene ◽  
Turkish Patients

Abstract The CHARGE (coloboma, heart defects, atresia, retardation, genital, ear) syndrome is a genetic disease characterized by ocular coloboma, choanal atresia or stenosis and semicircular canal abnormalities. Most of the patients clinically diagnosed with CHARGE syndrome have mutations in chromodomain helicase DNA-binding protein 7 (CHD7) gene. The CHD7 gene is located on chromosome 8q12.1, and up to now, there are more than 500 pathogenic mutations identified in the literature. We report two patients diagnosed with CHARGE syndrome with two novel mutations in the CHD7 gene: the first patient has double consecutive novel mutations in three adjacent codons, and the other has a novel insertion.

A candidate gene for choanal atresia in alpaca

Genome ◽  
2010 ◽  
Vol 53 (3) ◽  
pp. 224-230 ◽  
Author(s):  
Kent M. Reed ◽  
Miranda M. Bauer ◽  
Kristelle M. Mendoza ◽  
Aníbal G. Armién
Keyword(s):  
Regulatory Gene ◽  
Choanal Atresia ◽  
Clinical Manifestations ◽  
Charge Syndrome ◽  
Abnormal Development ◽  
Whole Genome Sequence ◽  
Sequence Difference ◽  
Coding Region ◽  
Human Sequence ◽  
Chd7 Gene

Choanal atresia (CA) is a common nasal craniofacial malformation in New World domestic camelids (alpaca and llama). CA results from abnormal development of the nasal passages and is especially debilitating to newborn crias. CA in camelids shares many of the clinical manifestations of a similar condition in humans (CHARGE syndrome). Herein we report on the regulatory gene CHD7 of alpaca, whose homologue in humans is most frequently associated with CHARGE. Sequence of the CHD7 coding region was obtained from a non-affected cria. The complete coding region was 9003 bp, corresponding to a translated amino acid sequence of 3000 aa. Additional genomic sequences corresponding to a significant portion of the CHD7 gene were identified and assembled from the 2× alpaca whole genome sequence, providing confirmatory sequence for much of the CHD7 coding region. The alpaca CHD7 mRNA sequence was 97.9% similar to the human sequence, with the greatest sequence difference being an insertion in exon 38 that results in a polyalanine repeat (A12). Polymorphism in this repeat was tested for association with CA in alpaca by cloning and sequencing the repeat from both affected and non-affected individuals. Variation in length of the poly-A repeat was not associated with CA. Complete sequencing of the CHD7 gene will be necessary to determine whether other mutations in CHD7 are the cause of CA in camelids.

scholarly journals Prenatal Sonographic Features of CHARGE Syndrome

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 415
Author(s):  
Kuntharee Traisrisilp ◽  
Wisit Chankhunaphas ◽  
Rekwan Sittiwangkul ◽  
Chureerat Phokaew ◽  
Vorasuk Shotelersuk ◽  
...  
Keyword(s):  
De Novo ◽  
Heart Defects ◽  
Molecular Genetic ◽  
Choanal Atresia ◽  
Charge Syndrome ◽  
Acoustic Stimulation ◽  
Genetic Mutation ◽  
Suspected Case ◽  
Autosomal Dominant Disorder ◽  
Canal Stenosis

CHARGE syndrome is a rare autosomal dominant disorder, associated with coloboma (C), heart defects (H), choanal atresia (A), retardation of growth and/or central nervous system (R), genitourinary anomalies (G) and ear abnormalities (E). Prenatal diagnosis of the syndrome is very rare but may be suspected when a combination of such abnormalities is identified. We describe a prenatally suspected case of CHARGE syndrome due to unique findings of cardiac defects (DORV) in combination with minor clues, including a structurally malformed ear with persistent non-response to an acoustic stimulation (which has never been prenatally described elsewhere), renal malrotation and growth restriction. Postnatal diagnosis was made based on confirmation of the prenatal findings and additional specific findings of bilateral coloboma, choanal atresia and ear canal stenosis. Finally, molecular genetic testing by whole exome sequencing of the neonate and her parents revealed a novel de novo heterozygous frameshift c.3506_3509dup variant in the CHD7 gene, confirming the clinical diagnosis of CHARGE syndrome. In conclusion, we describe unique prenatal features of CHARGE syndrome. Educationally, this is one of the rare examples of CHARGE syndrome, comprising all of the six specific anomalies as originally described; it is also supported by the identification of a specific genetic mutation. The identified genetic variant has never been previously reported, thereby expanding the mutational spectrum of CHD7. Finally, this case can inspire prenatal sonographers to increase awareness of subtle or minor abnormalities as genetic sonomarkers.

scholarly journals Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ting Chen ◽  
Haiying Wu ◽  
Chenxi Zhang ◽  
Jiarong Feng ◽  
Linqi Chen ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Homology Modelling ◽  
Gene Sequencing ◽  
Bioinformatic Analysis ◽  
Actin Binding ◽  
Clinical Genetics ◽  
Loss Of Function ◽  
Mineral Density ◽  
Trait Locus ◽  
The Impact

Background. Bone mineral density quantitative trait locus 18 (BMND18, OMIM #300910) is a type of early-onset osteogenesis imperfecta (OI) caused by loss-of-function mutations in the PLS3 gene, which encodes plastin-3, a key protein in the formation of actin bundles throughout the cytoskeleton. Here, we report a patient with PLS3 mutation caused BMND18 and evaluated all the reported disease-causing mutations by bioinformatic analysis. Methods. Targeted gene sequencing was performed to find the disease-causing mutation in our patient. Bioinformatic analyses mainly including homology modelling and molecular dynamics stimulation were conducted to explore the impact of the previously reported mutations on plastin-3. Results. Gene sequencing showed a novel nonsense mutation (c.745G > T, p.E249X), which locates at a highly conserved region containing residues p.240–266 (LOOP-1) in the PLS3 gene. Further bioinformatic analyses of the previously reported mutations revealed that LOOP-1 is predicted to physically connect the calponin-homology 1 (CH1) and CH2 domains of the ABD1 fragment and spatially locates within the interface of ABD1 and ABD2. It is crucial to the conformation transition and actin-binding function of plastin-3. Conclusions. This report identified a novel mutation that truncates the PLS3 gene. Moreover, bioinformatic analyses of the previous reported mutations in PLS3 gene lead us to find a critical LOOP-1 region of plastin-3 mutations at which may be detrimental to the integral conformation of plastin-3 and thus affect its binding to actin filament.

Identification of one novel CHD7 mutation in a patient from China with atypical CHARGE syndrome

Gene ◽  
2015 ◽  
Vol 571 (2) ◽  
pp. 298-302 ◽  
Author(s):  
Jian Cheng ◽  
Dingyuan Ma ◽  
Yun Wu ◽  
Chunyu Luo ◽  
Chengyi Huang ◽  
...  
Keyword(s):  
Charge Syndrome ◽  
Chd7 Mutation

scholarly journals Experience from clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families.

Heart ◽  
1997 ◽  
Vol 77 (2) ◽  
pp. 130-132 ◽  
Author(s):  
W. J. McKenna ◽  
P. Spirito ◽  
M. Desnos ◽  
O. Dubourg ◽  
M. Komajda
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Diagnostic Criteria ◽  
Clinical Genetics

Use of Steroid-Eluting Stents after Endoscopic Repair of Choanal Atresia: A Case Series with Review

2020 ◽  
Vol 129 (10) ◽  
pp. 1003-1010
Author(s):  
Lyndy J. Wilcox ◽  
Matthew M. Smith ◽  
Alessandro de Alarcon ◽  
Madison Epperson ◽  
Hayley Born ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Choanal Atresia ◽  
Case Series ◽  
Charge Syndrome ◽  
Primary Outcome Measure ◽  
Drug Eluting Stent ◽  
Inclusion Criteria ◽  
Endoscopic Repair ◽  
Surgical Interventions ◽  
Drug Eluting

Objective(s): To describe a single institution’s experience with the use of steroid-eluting stents after endoscopic transnasal repair of choanal atresia. Methods: A case series with review of children who underwent choanal atresia repair at a tertiary children’s hospital from June 2017 to January 2018 was performed. Those who had a mometasone drug-eluting stent (Propel® Mini, Intersect ENT Inc., Palo Alto, CA) placed after primary or secondary choanal atresia repair at our institution were included. The primary outcome measure was need for revision surgery due to stenosis. Postoperative regimens, duration of stenting, and need for return to the operating room (OR) were also assessed. Results: Five patients with a median age of 22 months at the time of repair met inclusion criteria. Two (40%) had bilateral atresia and 3 (60%) had confirmed CHARGE syndrome. A total of 6 mometasone drug-eluting stents were used in the 5 cases. Three patients were reassessed at least once in the OR; however, the majority (57.1%) of postoperative evaluations were able to be performed in the office or bedside setting. The first and last evaluations occurred a mean of 14 and 124 days after surgery, respectively. There were no instances of restenosis, repeat surgical interventions, or stent-related complications noted. Conclusion: Placement of a mometasone drug-eluting stent is a promising method to improve postoperative results and management of choanal atresia repair by limiting the need for repeat anesthetics and OR procedures, as well as the complications of traditional stents.

Diagnostics and therapy of bilateral choanal atresia in association with CHARGE syndrome

2020 ◽  
pp. 1-8
Author(s):  
T. Koppen ◽  
D. Bartmann ◽  
M. Jakob ◽  
F. Bootz ◽  
A. Müller ◽  
...  
Keyword(s):  
Choanal Atresia ◽  
Charge Syndrome ◽  
Diagnostics And Therapy
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