scholarly journals Distal hereditary motor neuropathy with vocal cord paresis: from difficulty in choral singing to a molecular genetic diagnosis

2016 ◽  
Vol 16 (3) ◽  
pp. 247-251 ◽  
Author(s):  
Gillian Ingram ◽  
Katy E S Barwick ◽  
Louise Hartley ◽  
Meriel McEntagart ◽  
Andrew H Crosby ◽  
...  
Keyword(s):  
Vocal Cord ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Motor Neuropathy ◽  
Choral Singing ◽  
Hereditary Motor ◽  
Vocal Cord Paresis ◽  
Hereditary Motor Neuropathy ◽  
Molecular Genetic Diagnosis

scholarly journals Genetic and Clinical Features in 24 Chinese Distal Hereditary Motor Neuropathy Families

2020 ◽  
Vol 11 ◽  
Author(s):  
Yongzhi Xie ◽  
Zhiqiang Lin ◽  
Pukar Singh Pakhrin ◽  
Xiaobo Li ◽  
Binghao Wang ◽  
...  
Keyword(s):  
Clinical Features ◽  
Genetic Diagnosis ◽  
Mainland China ◽  
Trna Synthetase ◽  
Motor Neuropathy ◽  
Variant Of Uncertain Significance ◽  
Hereditary Motor ◽  
Genes Encoding ◽  
Hereditary Motor Neuropathy ◽  
Uncertain Significance

Background and Objectives: Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies. The objectives of this study were to report the clinical and genetic features of dHMN patients in a Chinese cohort.Aims and Methods: We performed clinical assessments and whole-exome sequencing in 24 dHMN families from Mainland China. We conducted a retrospective analysis of the data and investigated the frequency and clinical features of patients with a confirmed mutation.Results: Two novel heterozygous mutations in GARS, c.373G>C (p.E125Q) and c.1015G>A (p.G339R), were identified and corresponded to the typical dHMN-V phenotype. Together with families with WARS, SORD, SIGMAR1, and HSPB1 mutations, 29.2% of families (7/24) acquired a definite genetic diagnosis. One novel heterozygous variant of uncertain significance, c.1834G>A (p.G612S) in LRSAM1, was identified in a patient with mild dHMN phenotype.Conclusion: Our study expanded the mutation spectrum of GARS mutations and added evidence that GARS mutations are associated with both axonal Charcot-Marie-Tooth and dHMN phenotypes. Mutations in genes encoding aminoamide tRNA synthetase (ARS) might be a frequent cause of autosomal dominant-dHMN, and SORD mutation might account for a majority of autosomal recessive-dHMN cases. The relatively low genetic diagnosis yield indicated more causative dHMN genes need to be discovered.

scholarly journals Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Hai-Lin Dong ◽  
Jia-Qi Li ◽  
Gong-Lu Liu ◽  
Hao Yu ◽  
Zhi-Ying Wu
Keyword(s):  
Ex Vivo ◽  
Protein Solubility ◽  
Chinese Patients ◽  
Hereditary Neuropathy ◽  
Motor Neuropathy ◽  
Causative Gene ◽  
Hereditary Motor ◽  
Functional Studies ◽  
Hereditary Motor Neuropathy

AbstractSorbitol dehydrogenase gene (SORD) has been identified as a novel causative gene of recessive forms of hereditary neuropathy, including Charcot–Marie–Tooth disease type 2 and distal hereditary motor neuropathy (dHMN). Our findings reveal two novel variants (c.404 A > G and c.908 + 1 G > C) and one known variant (c.757delG) within SORD in four Chinese dHMN families. Ex vivo cDNA polymerase chain reaction confirmed that c.908 + 1 G > C variant was associated with impaired splicing of the SORD transcript. In vitro cell functional studies showed that c.404 A > G variant resulted in aggregate formation of SORD and low protein solubility, confirming the pathogenicity of SORD variants. We have provided more evidence to establish SORD as a causative gene for dHMN.

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.

Distal hereditary motor neuropathy (DHMN): a new locus for an autosomal recessive form

2004 ◽  
Vol 9 (2) ◽  
pp. 122-123 ◽  
Author(s):  
ML Mostacciuolo ◽  
E Crestanello ◽  
F Boaretto ◽  
E Boscolo ◽  
M Liguori ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Motor Neuropathy ◽  
Hereditary Motor ◽  
Autosomal Recessive Form ◽  
Recessive Form ◽  
Hereditary Motor Neuropathy

Mitochondrial encephalopathies: molecular genetic diagnosis from blood samples

The Lancet ◽  
1991 ◽  
Vol 337 (8753) ◽  
pp. 1311-1313 ◽  
Author(s):  
S.R. Hammans ◽  
M.G. Sweeney ◽  
M. Brockington ◽  
J.A. Morgan-Hughes ◽  
A.E. Harding
Keyword(s):  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Blood Samples ◽  
Molecular Genetic Diagnosis

Characterising the phenotype and mode of inheritance of patients with inherited peripheral neuropathies carrying MME mutations

2018 ◽  
Vol 55 (12) ◽  
pp. 814-823 ◽  
Author(s):  
Vincenzo Lupo ◽  
Marina Frasquet ◽  
Ana Sánchez-Monteagudo ◽  
Ana Lara Pelayo-Negro ◽  
Tania García-Sobrino ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Late Onset ◽  
Axonal Neuropathy ◽  
Genetic Diagnosis ◽  
Hereditary Neuropathy ◽  
Motor Neuropathy ◽  
Charcot Marie Tooth Disease ◽  
Hereditary Motor Neuropathy ◽  
Index Cases ◽  
Mode Of Inheritance

BackgroundMutations in the metalloendopeptidase (MME) gene were initially identified as a cause of autosomal recessive Charcot-Marie-Tooth disease type 2 (CMT2). Subsequently, variants in MME were linked to other late-onset autosomal dominant polyneuropathies. Thus, our goal was to define the phenotype and mode of inheritance of patients carrying changes in MME.MethodsWe screened 197 index cases with a hereditary neuropathy of the CMT type or distal hereditary motor neuropathy (dHMN) and 10 probands with familial amyotrophic lateral sclerosis (fALS) using a custom panel of 119 genes. In addition to the index case subjects, we also studied other clinically and/or genetically affected and unaffected family members.ResultsWe found 17 variants in MME in a total of 20 index cases, with biallelic MME mutations detected in 13 cases from nine families (three in homozygosis and six in compound heterozygosis) and heterozygous variants found in 11 families. All patients with biallelic variants had a similar phenotype, consistent with late-onset axonal neuropathy. Conversely, the phenotype of patients carrying heterozygous mutations was highly variable [CMT type 1 (CMT1), CMT2, dHMN and fALS] and mutations did not segregate with the disease.ConclusionMME mutations that segregate in an autosomal recessive pattern are associated with a late-onset CMT2 phenotype, yet we could not demonstrate that MME variants in heterozygosis cause neuropathy. Our data highlight the importance of establishing an accurate genetic diagnosis in patients carrying MME mutations, especially with a view to genetic counselling.

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