scholarly journals Whole-Exome Sequencing in Idiopathic Short Stature: Rare Mutations Affecting Growth

2020 ◽  
Author(s):  
Shahab Noorian ◽  
Nami Mohammadian Khonsari ◽  
Shahram Savad ◽  
Benyamin Hakak-Zargar ◽  
Tessa Voth ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Treatment Options ◽  
Idiopathic Short Stature ◽  
Genetic Causes ◽  
Rare Mutations ◽  
Whole Exome ◽  
Common Diagnosis

AbstractIdiopathic short stature (ISS) is a common diagnosis of exclusion in patients with short stature (SS). We aimed to identify the genetic causes of SS in patients with ISS and investigate treatment options. Fourteen children with diagnosis of ISS were identified, and whole-exome sequencing (WES) was subsequently conducted on blood-derived DNA. Five patients were correctly diagnosed with ISS and four had rare mutations that have not been previously reported. Four patients had mutations known to cause SS and one had a mutation that was known not to affect height. WES can help identify rare mutations implicated in ISS.

scholarly journals Whole Exome Sequencing in Idiopathic Short Stature: Rare Mutations Affecting Growth

2020 ◽  
Author(s):  
Nami Mohammadian Khonsari ◽  
Shahab Noorian ◽  
Farzaneh Rohani ◽  
Sharham Savad ◽  
Kourosh Kabir ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Correct Diagnosis ◽  
Idiopathic Short Stature ◽  
Genetic Mutations ◽  
The Past ◽  
Rare Mutations ◽  
Whole Exome ◽  
Directing Attention

Abstract Introduction Evaluation of short stature is a challenge for pediatricians and in the process, idiopathic short stature (ISS) is an often diagnosis of exclusion. Non-pathogenetic mutations affecting height may present with phenotypes similar to the pathogenetic mutations. In this study, we aim to identify the underlying genetic cause of short stature in patients diagnosed with ISS and investigate potential treatments for them. Materials and Methods We identified 14 children in our practice who were under the age of 15 and were initially labelled as ISS. Then, we evaluated their plasma whole-exome sequencing (WES). Results Out of the 14 patients assessed with WES, five had normal results and correctly diagnosed with ISS. However, four of them had rare mutations that have not been extensively studied in the past. Due to the functions of these mutated genes and our patients’ phenotypes, we suspect that these mutations played a role in the short stature. Out of the remaining five patients, four had genetic mutations known to cause short stature and one had a mutation that was known not to affect height. Conclusion In patients who are initially diagnosed with ISS, WES can help to identify rare mutations that may play a role in short stature. Directing attention to these genes, may help with the correct diagnosis and choosing proper treatment for the patients.

scholarly journals Whole Exome Sequencing in Idiopathic Short Stature: rare mutations affecting growth

2019 ◽  
Author(s):  
Shahab Noorian ◽  
Farzaneh Rohani ◽  
Shahram Savad ◽  
Kourosh Kabir ◽  
Nami Mohammadian Khonsari ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Disorders ◽  
Correct Diagnosis ◽  
Test Results ◽  
Rare Mutations ◽  
Whole Exome ◽  
Common Causes ◽  
Blood Specimens

Abstract Introduction: one of the most common causes of referrals to paediatricians is short stature (ISS), some pathogenic mutations may present exactly similar to non-pathogenic causes, our goal is to identify and treat these patients labelled ISS with these mutations and hopefully treat them correctly. Materials and Methods: We assessed All children under the age of fifteen years labelled as ISS. Fourteen of them were confirmed to be ISS and thus were allowed in our study. Afterwards, we pooled their blood specimens and ordered a whole-exome sequencing (WES) test. Results: five patient had normal WES results. Four patients had rare motions that were not studied in the previous literature but due to the functions of the genes, and our patients’ phenotypes it is highly possible that these mutations caused our patients’ short stature. Four patients had known genetic mutations causing short stature. One patient had a mutation with no effect on height. With the help of WES, some rare mutations were found, with the patients’ phenotype and evaluation we identified their function, we diagnosed some other patients’ rare genetic disorders and assessed the possible effect of their mutation on their height and phenotype we aimed to determine how many children labelled as ISS are correctly diagnosed. By WES most of our patient achieved the correct diagnosis which would be impossible to diagnose without WES; thus the reason for their short stature was identified, with the correct diagnosis now we can aim for the proper treatment.

scholarly journals Diagnostic Whole Exome Sequencing in Patients with Short Stature

2018 ◽  
Author(s):  
Huijuan Zhu ◽  
Ziying Yang ◽  
Jun Sun ◽  
Wei Li ◽  
Hongbo Yang ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Utility ◽  
Molecular Diagnostic ◽  
Unknown Etiology ◽  
Growth Disorders ◽  
Pediatric Endocrinology ◽  
Genetic Causes ◽  
Whole Exome

AbstractShort stature is among the most common reasons for children being referred to the pediatric endocrinology clinics. The cause of short stature is broad, in which genetic factors play a substantial role, especially in primary growth disorders. However, identifying the molecular causes for short stature remains as a challenge because of the high heterogeneity of the phenotypes. Here, whole exome sequencing (WES) was used to identify the genetic causes of short stature with unknown etiology for 20 patients aged from 1 to 16 years old. The genetic causes of short stature were identified in 9 of the 20 patients, corresponding to a molecular diagnostic rate of 45%. Notably, in 2 of the 9 patients identified with genetic causes, the diagnosed diseases based on WES are different from the original clinical diagnosis. Our results highlight the clinical utility of WES in the diagnosis of rare, high heterogeneity disorders.

scholarly journals Whole Exome Sequencing to Identify Genetic Causes of Short Stature

2014 ◽  
Vol 82 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Michael H. Guo ◽  
Yiping Shen ◽  
Emily C. Walvoord ◽  
Timothy C. Miller ◽  
Jennifer E. Moon ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Causes ◽  
Whole Exome

scholarly journals Genetic causes of cardiomyopathies identified by Whole Exome Sequencing

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. 2605-2605
Author(s):  
B. Tomberli ◽  
F. Girolami ◽  
S. Bardi ◽  
M. Benelli ◽  
E. Contini ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Causes ◽  
Whole Exome

Juberg-Hayward syndrome is a cohesinopathy, caused by mutation in ESCO2

2020 ◽  
Author(s):  
Piranit Nik Kantaputra ◽  
Prapai Dejkhamron ◽  
Worrachet Intachai ◽  
Chumpol Ngamphiw ◽  
Katsushige Kawasaki ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Upper Limb ◽  
Autosomal Recessive ◽  
Cleft Lip ◽  
Clinical Findings ◽  
Protein Model ◽  
Whole Exome ◽  
Cleft Lip Palate

Summary Background Juberg-Hayward syndrome (JHS; MIM 216100) is a rare autosomal recessive malformation syndrome, characterized by cleft lip/palate, microcephaly, ptosis, short stature, hypoplasia or aplasia of thumbs, and dislocation of radial head and fusion of humerus and radius leading to elbow restriction. Objective To report for the first time the molecular aetiology of JHS. Patient and methods Clinical and radiographic examination, whole exome sequencing, Sanger sequencing, mutant protein model construction, and in situ hybridization of Esco2 expression in mouse embryos were performed. Results Clinical findings of the patient consisted of repaired cleft lip/palate, microcephaly, ptosis, short stature, delayed bone age, hypoplastic fingers and thumbs, clinodactyly of the fifth fingers, and humeroradial synostosis leading to elbow restriction. Intelligence is normal. Whole exome sequencing of the whole family showed a novel homozygous base substitution c.1654C>T in ESCO2 of the proband. The sister was homozygous for the wildtype variant. Parents were heterozygous for the mutation. The mutation is predicted to cause premature stop codon p.Arg552Ter. Mutations in ESCO2, a gene involved in cohesin complex formation, are known to cause Roberts/SC phocomelia syndrome. Roberts/SC phocomelia syndrome and JHS share similar clinical findings, including autosomal recessive inheritance, short stature, cleft lip/palate, severe upper limb anomalies, and hypoplastic digits. Esco2 expression during the early development of lip, palate, eyelid, digits, upper limb, and lower limb and truncated protein model are consistent with the defect. Conclusions Our study showed that Roberts/SC phocomelia syndrome and JHS are allelic and distinct entities. This is the first report demonstrating that mutation in ESCO2 causes JHS, a cohesinopathy.

scholarly journals Pathogenic variants identified by whole-exome sequencing in 43 patients with epilepsy

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Linlin Zhang ◽  
Jinshuang Gao ◽  
Hailiang Liu ◽  
Yuan Tian ◽  
Xiaoli Zhang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Diagnostic Yield ◽  
Treatment Options ◽  
Molecular Genetic ◽  
Epileptic Encephalopathy ◽  
Molecular Genetic Analysis ◽  
Specific Diagnosis ◽  
Whole Exome ◽  
Early Establishment

Abstract Background Epilepsy is a group of neurological disorders characterized by recurrent epileptic seizures. Epilepsy is affected by many factors, approximately 20–30% of cases are caused by acquired conditions, but in the remaining cases, genetic factors play an important role. Early establishment of a specific diagnosis is important to treat and manage this disease. Methods In this study, we have recruited 43 epileptic encephalopathy patients and the molecular genetic analysis of those children was performed by whole-exome sequencing (WES). Results Fourteen patients (32.6%, 14/43) had positive genetic diagnoses, including fifteen mutations in fourteen genes. The overall diagnostic yield was 32.6%. A total of 9 patients were diagnosed as pathogenic mutations, including 4 variants had been reported as pathogenic previously and 6 novel variants that had not been reported previously. Therefore, WES heralds promise as a tool for clinical diagnosis of patients with genetic disease. Conclusion Early establishment of a specific diagnosis, on the one hand, is necessary for providing an accurate prognosis and recurrence risk as well as optimizing management and treatment options. On the other hand, to unveil the genetic architecture of epilepsy, it is of vital importance to investigate the phenotypic and genetic complexity of epilepsy.

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