Charcot–Marie–Tooth Disease type 4C: Novel mutations, clinical presentations, and diagnostic challenges

Jerath, Nivedita U.; Mankodi, Ami; Crawford, Thomas O.; Baloui, Hasna; Nnamdi-Emeratom, Chioma; Schindler, Alice B.; Heiman‐Patterson, Terry; Chrast, Roman; Shy, Michael E.

doi:10.1002/mus.25981

Cited by 14 publications

(9 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 9 The SH3TC2 gene encodes a protein with two SH3 domains and ten tetratricopeptide repeats 2 (TC2) motifs, involved in the myelin layer formation by the Schwann cells. 10 SH3TC2 mutations disrupt the interaction with GTPase (guanosine triphosphatase) Rab11, a key regulator in recycling the endosome functions, resulting in impaired myelination by Schwann cells as this SH3TC2/Rab11 interaction is required for normal myelination. 11 CMT4C has an autosomal recessive mode of Mendelian inheritance.…”

Section: Discussionmentioning

confidence: 99%

“…12 The phenotypic variability and associations of CMT4C may be due to the cryptogenic modifiers or the SH3TC2 protein diversity. 10 In 2015, Kalane et al 13 reported the first case of CMT4C in a 10-year-old Indian girl with a homozygous nonsense variation c. 2710C > T in exon 11 of the SH3TC2 gene, with bilateral mild pes cavus foot deformities without any spinal deformity. In 2018, Jerath et al 10 reported associations of CMT4C with other rare diseases such as Von-Willebrand disease type 2M, short-chain acyl-coenzyme A dehydrogenase deficiency, retinitis pigmentosa, and plasminogen activator inhibitor-1 deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…10 In 2015, Kalane et al 13 reported the first case of CMT4C in a 10-year-old Indian girl with a homozygous nonsense variation c. 2710C > T in exon 11 of the SH3TC2 gene, with bilateral mild pes cavus foot deformities without any spinal deformity. In 2018, Jerath et al 10 reported associations of CMT4C with other rare diseases such as Von-Willebrand disease type 2M, short-chain acyl-coenzyme A dehydrogenase deficiency, retinitis pigmentosa, and plasminogen activator inhibitor-1 deficiency. In 2022, Lorenzoni et al 14 reported the association of CMT4C and myasthenia gravis in a 10-year-old girl ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Charcot-Marie-Tooth Disease Type 4C and Autosomal Dominant Heterozygous Ichthyosis Vulgaris, with Bilateral Hearing Loss: A Novel Association with Review of Literature

et al. 2022

View full text Add to dashboard Cite

A 3-year-old boy, firstborn to nonconsanguineous parents, presented with motor development delay and floppiness of bilateral lower limbs since birth. No significant family history presented at time of check-up. He could stand with support, eat with a spoon without spillage, and speak in two-word sentences. There was no history suggestive of cranial nerve impairment. Examination revealed normal head circumference, dry, scaly skin lesions on the trunk, distal weakness with sluggish deep tendon reflexes in bilateral lower limbs, and a high stepping gait. Nerve conduction studies revealed demyelinating polyneuropathy. Brain stem-evoked response audiometry testing revealed auditory neuropathy. Clinical exome sequencing revealed a known pathogenic variant of 3325C > T in the SH3TC2 gene suggestive of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris with a novel variant of 2218C > T in the FLG gene. We have reviewed the available literature for reported associations of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris. This is probably the first reported association of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris with bilateral hearing loss.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Charcot-Marie-Tooth Disease Type 4C and Autosomal Dominant Heterozygous Ichthyosis Vulgaris, with Bilateral Hearing Loss: A Novel Association with Review of Literature

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The phenotype of patient S.11 with homozygous SH3TC2 variants and CMT4C has been reported. 13 An adult female (S.15) with a PNPLA6 variant had juvenile-onset MND with distal weakness most marked in finger flexion, ankle dorsiflexion and toe extension.…”

Section: Clinical Presentations In Patients With Novel Pathogenic Variantsmentioning

confidence: 99%

Improving the efficacy of exome sequencing at a quaternary care referral centre: novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases

Sarkar

Owen

et al. 2021

J Neurol Neurosurg Psychiatry

Self Cite

View full text Add to dashboard Cite

BackgroundWe used a multimodal approach including detailed phenotyping, whole exome sequencing (WES) and candidate gene filters to diagnose rare neurological diseases in individuals referred by tertiary neurology centres.MethodsWES was performed on 66 individuals with neurogenetic diseases using candidate gene filters and stringent algorithms for assessing sequence variants. Pathogenic or likely pathogenic missense variants were interpreted using in silico prediction tools, family segregation analysis, previous publications of disease association and relevant biological assays.ResultsMolecular diagnosis was achieved in 39% (n=26) including 59% of childhood-onset cases and 27% of late-onset cases. Overall, 37% (10/27) of myopathy, 41% (9/22) of neuropathy, 22% (2/9) of MND and 63% (5/8) of complex phenotypes were given genetic diagnosis. Twenty-seven disease-associated variants were identified including ten novel variants in FBXO38, LAMA2, MFN2, MYH7, PNPLA6, SH3TC2 and SPTLC1. Single-nucleotide variants (n=10) affected conserved residues within functional domains and previously identified mutation hot-spots. Established pathogenic variants (n=16) presented with atypical features, such as optic neuropathy in adult polyglucosan body disease, facial dysmorphism and skeletal anomalies in cerebrotendinous xanthomatosis, steroid-responsive weakness in congenital myasthenia syndrome 10. Potentially treatable rare diseases were diagnosed, improving the quality of life in some patients.ConclusionsIntegrating deep phenotyping, gene filter algorithms and biological assays increased diagnostic yield of exome sequencing, identified novel pathogenic variants and extended phenotypes of difficult to diagnose rare neurogenetic disorders in an outpatient clinic setting.

show abstract

Treatment of Charcot-Marie-Tooth neuropathies

Beloribi-Djefaflia

Attarian

2023

Revue Neurologique

View full text Add to dashboard Cite

Charcot–Marie–Tooth Disease type 4C: Novel mutations, clinical presentations, and diagnostic challenges

Cited by 14 publications

References 30 publications

Charcot-Marie-Tooth Disease Type 4C and Autosomal Dominant Heterozygous Ichthyosis Vulgaris, with Bilateral Hearing Loss: A Novel Association with Review of Literature

Charcot-Marie-Tooth Disease Type 4C and Autosomal Dominant Heterozygous Ichthyosis Vulgaris, with Bilateral Hearing Loss: A Novel Association with Review of Literature

Improving the efficacy of exome sequencing at a quaternary care referral centre: novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases

Treatment of Charcot-Marie-Tooth neuropathies

Contact Info

Product

Resources

About