scholarly journals Improvement of diagnostic yield in carbamoylphosphate synthetase 1 ( CPS1 ) molecular genetic investigation by RNA sequencing

JIMD Reports ◽  
2020 ◽  
Vol 52 (1) ◽  
pp. 28-34
Author(s):  
Jasmine Isler ◽  
Véronique Rüfenacht ◽  
Corinne Gemperle ◽  
Gabriella Allegri ◽  
Johannes Häberle
Keyword(s):  
Rna Sequencing ◽  
Diagnostic Yield ◽  
Molecular Genetic ◽  
Genetic Investigation ◽  
Carbamoylphosphate Synthetase

Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism

2020 ◽  
Vol 33 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tatsushi Tanaka ◽  
Kohei Aoyama ◽  
Atsushi Suzuki ◽  
Shinji Saitoh ◽  
Haruo Mizuno
Keyword(s):  
Congenital Hypothyroidism ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Japanese Patients ◽  
Thyroid Stimulating Hormone ◽  
Allelic Variant ◽  
Genetic Investigation ◽  
Pathogenic Variants ◽  
Recessive Genes ◽  
Molecular Genetic Diagnosis

AbstractObjectivesCongenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.MethodsWe enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.ResultsWe identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants.ConclusionsThe prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.

A Korean Patient with Early Juvenile Form of Metachromatic Leukodystrophy: Biochemical and Molecular Genetic Investigation

2017 ◽  
Vol 7 (1) ◽  
pp. 41
Author(s):  
Yeong-Bin Kim ◽  
Hyung-Doo Park ◽  
Rihwa Choi ◽  
Soo-Youn Lee ◽  
Chang-Seok Ki ◽  
...  
Keyword(s):  
Metachromatic Leukodystrophy ◽  
Molecular Genetic ◽  
Genetic Investigation ◽  
Juvenile Form ◽  
Early Juvenile ◽  
Korean Patient

scholarly journals Transspecies beak color polymorphism in the Darwin’s finch radiation

2021 ◽  
Author(s):  
Erik D. Enbody ◽  
C. Grace Sprehn ◽  
Arhat Abzhanov ◽  
Huijuan Bi ◽  
Mariya P. Dobreva ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Introgressive Hybridization ◽  
Color Polymorphism ◽  
Regulatory Mutation ◽  
Genetic Investigation ◽  
Interspecific Introgression ◽  
Evolutionary Diversification ◽  
Ecological Selection ◽  
Balanced Polymorphism ◽  
As Species

AbstractCarotenoid-based polymorphisms are widespread in populations of birds, fish, and reptiles1, but little is known of how they affect fitness and are maintained as species multiply2. We report a combined field and molecular-genetic investigation of a nestling beak color polymorphism in Darwin’s finches. Beaks are pink or yellow, and yellow is recessive3. Here we show that the polymorphism arose in the Galápagos approximately half a million years ago through a regulatory mutation in the BCO2 gene, and is shared by 14 descendant species. The frequency of the yellow genotype is associated with cactus flower abundance in cactus finches, and is altered by introgressive hybridization. The polymorphism is most likely a balanced polymorphism, maintained by ecological selection pressures associated with diet, and augmented by occasional interspecific introgression. Polymorphisms that are hidden as adults, as here, may contribute to evolutionary diversification in underappreciated ways in other systems.

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.

scholarly journals Utilization and Diagnostic Yield of Neurogenetic Testing at a Tertiary Care Facility

2007 ◽  
Vol 53 (6) ◽  
pp. 1016-1022 ◽  
Author(s):  
Kerstin L Edlefsen ◽  
Jonathan F Tait ◽  
Mark H Wener ◽  
Michael Astion
Keyword(s):  
Positive Result ◽  
Diagnostic Yield ◽  
Medical Center ◽  
Care Center ◽  
Academic Medical Center ◽  
Molecular Genetic ◽  
Tertiary Care ◽  
Care Facility ◽  
Utilization Review ◽  
Tertiary Care Facility

Abstract Background: Institutions face increasing charges related to molecular genetic testing for neurological diseases. The literature contains little information on the utilization and performance of these tests. Methods: A retrospective utilization review was performed to determine the diagnostic yield of neurogenetic tests ordered during calendar year 2005 at a large academic medical center in the western United States. Results: Overall, a relevant mutation was identified in 30.2% of the 162 patients tested and in 21.5% of the 121 probands, defined as patients for whom no mutation has been previously identified in a family member. Patients with muscle weakness (n = 65) had a mutation detected in 26.2% of all patients and 23.5% of probands (n = 51), with an estimated testing cost per positive result of $3190. Patients tested for neuropathy (n = 36) had a mutation detected in 27.8% of patients and 22.6% of probands (n = 31), with an estimated cost per positive result of $5955. Patients with chorea (n = 25) had a positive result obtained in 68% of patients and 71.4% of probands (n = 7); the estimated cost per positive test was $440. Other diagnostic categories evaluated include ataxias (n = 18; yield, 11.1%; $7620 per positive), familial stroke or dementia syndromes (n = 8; yield, 12.5%; $6760 per positive), and multisystem mitochondrial disorders (n = 10; yield, 20%; $6485 per positive). Conclusions: Expert clinicians at a tertiary care center who ordered neurogenetic tests obtained a positive result in 21.5% of patients without previously identified familial mutations. These results can be used for comparison and to help establish utilization guidelines for neurogenetic testing.

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