scholarly journals Bi-allelic variants in MTMR5/SBF1 cause Charcot-Marie-Tooth type 4B3 featuring mitochondrial dysfunction

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Beatrice Berti ◽  
Giovanna Longo ◽  
Francesco Mari ◽  
Stefano Doccini ◽  
Ilaria Piccolo ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mitochondrial Dysfunction ◽  
Early Onset ◽  
Integrated Approach ◽  
Compound Heterozygous ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Pathogenic Variants ◽  
First Case ◽  
Spine Mri

Abstract Background Charcot-Marie-Tooth disease (CMT) type 4B3 (CMT4B3) is a rare form of genetic neuropathy associated with variants in the MTMR5/SBF1 gene. MTMR5/SBF1 is a pseudophosphatase predicted to regulate endo-lysosomal trafficking in tandem with other MTMRs. Although almost ubiquitously expressed, pathogenic variants primarily impact on the peripheral nervous system, corroborating the involvement of MTMR5/SBF1 and its molecular partners in Schwann cells-mediated myelinization. Case presentation We report a case of severe CMT4B3 characterized by early-onset motor and axonal polyneuropathy in an Italian child in absence of any evidence of brain and spine MRI abnormalities or intellectual disability and with a biochemical profile suggestive of mitochondrial disease. Using an integrated approach combining both NGS gene panels and WES analysis, we identified two novel compound heterozygous missense variants in MTMR5/SBF1 gene, p.R763H (c.2291G > A) and p.G1064E (c.3194G > A). Studies in muscle identified partial defects of oxidative metabolism. Conclusion We describe the first case of an early onset severe polyneuropathy with motor and axonal involvement, due to recessive variants in the MTMR5/SBF1 gene, with no evidence of brain and spine MRI abnormalities, intellectual disability, no clinical and neurophysiological evidences of distal sensory impairment, and rapid neuromuscular deterioration. This report suggests that MTMR5/SBF1 should be considered in cases of infantile-onset CMT with secondary mitochondrial dysfunction.

The First Case Report of Kabuki Syndrome from the National Iranian Registry of Primary Immunodeficiencies

2021 ◽  
Vol 21 ◽  
Author(s):  
Molood Safarirad ◽  
Ali Abbaszadeh Ganji ◽  
Saba Fekrvand ◽  
Reza Yazdani ◽  
Ahmad Vosughi Motlagh ◽  
...  
Keyword(s):  
Congenital Anomaly ◽  
Intellectual Disability ◽  
Definitive Diagnosis ◽  
Facial Features ◽  
Kabuki Syndrome ◽  
Rare Congenital Anomaly ◽  
Dysmorphic Features ◽  
Pathogenic Variants ◽  
First Case ◽  
Whole Exome

: Kabuki syndrome is a rare congenital anomaly/mental retardation syndrome characterized by intellectual disability, developmental delay, short stature, facial dysmorphic features including ectropion of the lateral third of the lower eyelids and long palpebral fissures, and prominent finger pads. Pathogenic variants of KMT2D (MLL2) and KDM6A are found to be the major causes of Kabuki syndrome. Here, we report the first Iranian case with Kabuki syndrome with an IQ of 79, two episodes of viral pneumonia and distinctive facial features, prominent ears and persistent fetal fingertip pads. These characteristics raised our suspicion for performing whole-exome sequencing (WES), which revealed 2 heterozygous pathogenic missense variants in the KMT2D gene: c.C10024T in exon 34 leading to p.R3342C and c.G15005A in exon 48 leading to p.R5002Q. Hence, the definitive diagnosis of Kabuki syndrome was made based on molecular findings along with the intellectual disability and characteristic facial features.

Compound heterozygous mutations of SH3TC2 in Charcot–Marie–Tooth disease type 4C patients

2019 ◽  
Vol 64 (9) ◽  
pp. 961-965 ◽  
Author(s):  
Ah Jin Lee ◽  
Soo Hyun Nam ◽  
Jin-Mo Park ◽  
Sumaira Kanwal ◽  
Yu Jin Choi ◽  
...  
Keyword(s):  
Disease Type ◽  
Compound Heterozygous ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Compound Heterozygous Mutations ◽  
Tooth Disease

scholarly journals Novel mutation in the periaxin gene causal to Charcot–Marie–Tooth disease type 4F

2019 ◽  
Vol 48 (2) ◽  
pp. 030006051986206
Author(s):  
Yu-hui Chen ◽  
Hua Zhang ◽  
Ling-bing Meng ◽  
Xiao-yan Tang ◽  
Tao Gong ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Chinese Patients ◽  
Homozygous Mutation ◽  
Hereditary Neuropathy ◽  
Limb Weakness ◽  
Pes Cavus ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Protein Levels ◽  
First Case

Charcot–Marie–Tooth (CMT) disease is the most common hereditary neuropathy. Mutations in the periaxin gene ( PRX) can cause CMT type 4F, an autosomal recessive neuropathy, which is clinically characterized by slowly progressive distal muscle atrophy and weakness, with pes cavus deformity of the foot, and the absence of deep tendon reflexes. To date, dozens of reports of PRX mutations have been published worldwide, but none have been reported in Chinese patients. Here, we describe a 14-year-old Chinese boy with neuropathy characterized by slowly progressive limb weakness and atrophy, as well as sensory ataxia, whose cerebrospinal protein levels were 1627 mg/L. Genetic analysis identified a novel homozygous mutation, c.1174C>T (p.R392X), in exon 6 of PRX, which is the first case of its kind recorded in China.

Mitochondrial dysfunction and pathophysiology of Charcot–Marie–Tooth disease involving GDAP1 mutations

2011 ◽  
Vol 227 (1) ◽  
pp. 31-41 ◽  
Author(s):  
Julien Cassereau ◽  
Arnaud Chevrollier ◽  
Naïg Gueguen ◽  
Valérie Desquiret ◽  
Christophe Verny ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

Autosomal Recessive Axonal Form of Charcot-Marie-Tooth Disease Caused by Compound Heterozygous 3′-Splice Site and Ser130Cys Mutation in theGDAP1Gene

2005 ◽  
Vol 36 (3) ◽  
pp. 206-209 ◽  
Author(s):  
D. Kabzińska ◽  
A. Kochański, ◽  
H. Drac ◽  
B. Ryniewicz ◽  
K. Rowińska-Marcińska ◽  
...  
Keyword(s):  
Splice Site ◽  
Autosomal Recessive ◽  
Compound Heterozygous ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth Disease

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0133423 ◽  
Author(s):  
Yi-Chu Liao ◽  
Yo-Tsen Liu ◽  
Pei-Chien Tsai ◽  
Chia-Ching Chang ◽  
Yen-Hua Huang ◽  
...  
Keyword(s):  
Early Onset ◽  
De Novo ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals Compound heterozygous PMP22 deletion mutations causing severe Charcot–Marie–Tooth disease type 1

2010 ◽  
Vol 55 (11) ◽  
pp. 771-773 ◽  
Author(s):  
Akiko Abe ◽  
Kazuyuki Nakamura ◽  
Mitsuhiro Kato ◽  
Chikahiko Numakura ◽  
Tomomi Honma ◽  
...  
Keyword(s):  
Disease Type ◽  
Compound Heterozygous ◽  
Charcot Marie Tooth ◽  
Deletion Mutations ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals Mutations in both SAMD9 and SLC19A2 genes caused complex phenotypes characterized by recurrent infection, dysphagia and profound deafness – a case report for dual diagnosis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yan Zhang ◽  
Yi Zhang ◽  
Victor Wei Zhang ◽  
Chunyi Zhang ◽  
Hongke Ding ◽  
...  
Keyword(s):  
De Novo ◽  
Vitamin B1 ◽  
Recurrent Infection ◽  
Multiple Organ ◽  
Growth Delay ◽  
Compound Heterozygous ◽  
Mendelian Disease ◽  
Pathogenic Variants ◽  
First Case ◽  
Low Incidence

Abstract Background Phenotypic difference is general in Mendelian disease. Due to the extremely low incidence for a single disease, phenotype spectrum needs to be expanded. Meanwhile, earlier knowledge says patients who suffered from two kinds of different Mendelian disease are very rare. Case presentation We describe a case of neonatal male with genital anomalies, growth delay, skin hyperpigmentation, chronic lung disease with recurrent infection, anemia, and severe deafness. Without any clear etiology after routine workflow, whole exome sequencing was carried on. A pathogenic de novo SAMD9 mutation and compound heterozygous likely-pathogenic variants in SLC19A2 were identified. Some symptoms were improved after the patient was treated with vitamin B1. Unfortunately, the boy died from sepsis and multiple organ failure before 1 year old. Conclusion Combining the phenotype and clinical progress of treatment, we report that it is the first case of a patient with both MIRAGE syndrome and TRMA syndrome.

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