scholarly journals Compound Heterozygous CHAT Gene Mutations of a Large Deletion and a Missense Variant in a Chinese Patient With Severe Congenital Myasthenic Syndrome With Episodic Apnea

2019 ◽  
Vol 10 ◽  
Author(s):  
Zhimei Liu ◽  
Li Zhang ◽  
Danmin Shen ◽  
Changhong Ding ◽  
Xinying Yang ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Missense Variant ◽  
Large Deletion ◽  
Chinese Patient ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Myasthenic Syndrome

scholarly journals A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 821
Author(s):  
Olga Shchagina ◽  
Ludmila Bessonova ◽  
Igor Bychkov ◽  
Tatiana Beskorovainaya ◽  
Aleksander Poliakov
Keyword(s):  
Uniparental Disomy ◽  
Missense Variant ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Chromosome 2 ◽  
Loss Of Function ◽  
Maternal Uniparental Disomy ◽  
Healthy Sibling ◽  
Myasthenic Syndrome ◽  
The Moment

Congenital myasthenic syndrome-22 (CMS22, OMIM 616224) is a very rare recessive hereditary disorder. At the moment, ten CMS22 patients are described, with the disorder caused by nine different Loss-of-Function mutations and 14 gross deletions in the PREPL gene. The materials for our study were DNA samples of five family members: two patients with myasthenia, their healthy sibling and parents. Clinical exome analysis was carried out for one patient, then the whole family was checked for target variants with Sanger sequencing, quantitative multiplex ligation-dependent probe amplification, and chromosome 2 microsatellite markers study. To determine the functional significance of the splicing variant, we applied the minigene assay. The cause of the proband’s disorder is a compound heterozygous state of two previously non-described pathogenic PREPL variants: a c.1528C>T (p.(Arg510Ter)) nonsense mutation and a c.2094G>T pseudo-missense variant, which, simultaneously with a p.(Lys698Asn) amino acid substitution, affects splicing, leading to exon 14 skipping in mRNA. The second patient’s disorder was caused by a homozygous nonsense c.1528C>T (p.(Arg510Ter)) mutation due to maternal uniparental disomy (UPD) of chromosome 2. In this study, we describe a unique case, in which two siblings with a rare disorder have different pathologic genotypes.

scholarly journals A Novel Missense Variant in the AGRN Gene; Congenital Myasthenic Syndrome Presenting With Head Drop

2017 ◽  
Vol 18 (3) ◽  
pp. 147-151 ◽  
Author(s):  
Mert Karakaya ◽  
Ozge Ceyhan-Birsoy ◽  
Alan H. Beggs ◽  
Haluk Topaloglu
Keyword(s):  
Missense Variant ◽  
Congenital Myasthenic Syndrome ◽  
Myasthenic Syndrome

scholarly journals Two Novel HOGA1 Splicing Mutations Identified in a Chinese Patient with Primary Hyperoxaluria Type 3

2015 ◽  
Vol 42 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Xinsheng Wang ◽  
Xiangzhong Zhao ◽  
Xiaoling Wang ◽  
Jian Yao ◽  
Feifei Zhang ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Gene Mutations ◽  
Primary Hyperoxaluria ◽  
Mutant Gene ◽  
Chinese Patient ◽  
Compound Heterozygous ◽  
Sequencing Analysis ◽  
Exon Trapping ◽  
Primary Hyperoxaluria Type 3 ◽  
Type 3

Background: Twenty-six HOGA1 mutations have been reported in primary hyperoxaluria (PH) type 3 (PH3) patients with c.700 + 5G>T accounting for about 50% of the total alleles. However, PH3 has never been described in Asians. Methods: A Chinese child with early-onset nephrolithiasis was suspected of having PH. We searched for AGXT, GRHPR and HOGA1 gene mutations in this patient and his parents. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. Results: Two heterozygous mutations not previously described in the literature about HOGA1 were identified (compound heterozygous). One mutation was a successive 2 bp substitution at the last nucleotide of exon 6 and at the first nucleotide of intron 6, respectively (c.834_834 + 1GG>TT), while the other one was a guanine to adenine substitution of the last nucleotide of exon 6 (c.834G>A). Direct sequencing analysis failed to find these mutations in 100 unrelated healthy subjects and the functional role on splicing of both variants found in this study was confirmed by a minigene assay based on the pSPL3 exon trapping vector. In addition, we found a SNP in this family (c.715G>A, p.V239I). There were no mutations detected in AGXT and GRHPR. Conclusion: Two novel HOGA1 mutations were identified in association with PH3. This is the first description and investigation on mutant gene analysis of PH3 in an Asian.

scholarly journals Congenital myasthenic syndrome in a cohort of patients with ‘double’ seronegative myasthenia gravis

2021 ◽  
Author(s):  
Paulo José Lorenzoni ◽  
Renata Dal-Pra Ducci ◽  
Raquel Cristina Arndt ◽  
Nyvia Milicio Coblinski Hrysay ◽  
Otto Jesus Hernandez Fustes ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Myasthenia Gravis ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Previous Diagnosis ◽  
Seronegative Myasthenia Gravis ◽  
Single Center Study ◽  
Myasthenic Syndrome ◽  
Compound Heterozygous Variants ◽  
Brazilian Cohort

ABSTRACT Background: Congenital myasthenic syndromes (CMS) have some phenotypic overlap with seronegative myasthenia gravis (SNMG). Objective: The aim of this single center study was to assess the minimum occurrence of CMS misdiagnosed as double SNMG in a Brazilian cohort. Methods: The genetic analysis of the most common mutations in CHRNE, RAPSN, and DOK7 genes was used as the main screening tool. Results: We performed genetic analysis in 22 patients with a previous diagnosis of ‘double’ SNMG. In this study, one CMS patient was confirmed due to the presence of compound heterozygous variants in the CHRNE gene (c.130insG/p.Cys210Phe). Conclusions: This study confirmed that CMS due to CHNRE mutations can be mistaken for SNMG. In addition, our study estimated the prevalence of misdiagnosed CMS to be 4.5% in ‘double’ SNMG patients of our center. Based on our findings, genetic screening could be helpful in the diagnostic workup of patients with ‘double’ SNMG in whom differential diagnosis is recommended.

scholarly journals CHRNE compound heterozygous mutations in congenital myasthenic syndrome

Medicine ◽  
2018 ◽  
Vol 97 (17) ◽  
pp. e0347
Author(s):  
Kunfang Yang ◽  
Hongyi Cheng ◽  
Fang Yuan ◽  
Linyi Meng ◽  
Rongrong Yin ◽  
...  
Keyword(s):  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Myasthenic Syndrome ◽  
Compound Heterozygous Mutations

Novel compound heterozygous PANK2 gene mutations in a Chinese patient with atypical pantothenate kinase-associated neurodegeneration

2018 ◽  
Vol 128 (12) ◽  
pp. 1109-1113 ◽  
Author(s):  
Yuan Cheng ◽  
Yu-tao Liu ◽  
Zhi-hua Yang ◽  
Jing Yang ◽  
Chang-he Shi ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Chinese Patient ◽  
Compound Heterozygous ◽  
Pantothenate Kinase

scholarly journals Presynaptic congenital myasthenic syndrome with altered synaptic vesicle homeostasis linked to compound heterozygous sequence variants in RPH3A

2018 ◽  
Vol 6 (3) ◽  
pp. 434-440 ◽  
Author(s):  
Ricardo A. Maselli ◽  
Jessica Vázquez ◽  
Leah Schrumpf ◽  
Juan Arredondo ◽  
Marian Lara ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Congenital Myasthenic Syndrome ◽  
Compound Heterozygous ◽  
Sequence Variants ◽  
Myasthenic Syndrome

scholarly journals FANCA Gene Mutations in North African Fanconi Anemia Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Abir Ben Haj Ali ◽  
Olfa Messaoud ◽  
Sahar Elouej ◽  
Faten Talmoudi ◽  
Wiem Ayed ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Genetic Disorders ◽  
Gene Mutations ◽  
Missense Variant ◽  
High Rate ◽  
Compound Heterozygous ◽  
North African ◽  
Founder Mutations ◽  
Molecular Approaches ◽  
Number Of Patients

Populations in North Africa (NA) are characterized by a high rate of consanguinity. Consequently, the proportion of founder mutations might be higher than expected and could be a major cause for the high prevalence of recessive genetic disorders like Fanconi anemia (FA). We report clinical, cytogenetic, and molecular characterization of FANCA in 29 North African FA patients from Tunisia, Libya, and Algeria. Cytogenetic tests revealed high rates of spontaneous chromosome breakages for all patients except two of them. FANCA molecular analysis was performed using three different molecular approaches which allowed us to identify causal mutations as homozygous or compound heterozygous forms. It included a nonsense mutation (c.2749C > T; p.Arg917Ter), one reported missense mutation (c.1304G > A; p.Arg435His), a novel missense variant (c.1258G > A; p.Asp409Glu), and the FANCA most common reported mutation (c.3788_3790delTCT; p.Phe1263del). Furthermore, three founder mutations were identified in 86.7% of the 22 Tunisian patients: (1) a deletion of exon 15, in 36.4% patients (8/22); (2), a deletion of exons 4 and 5 in 23% (5/22) and (3) an intronic mutation c.2222 + 166G > A, in 27.3% (6/22). Despite the relatively small number of patients studied, our results depict the mutational landscape of FA among NA populations and it should be taken into consideration for appropriate genetic counseling.

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