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Gene: GJB1

Green List (high evidence)

OMIM: "Charcot-Marie-Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory peripheral neuropathies. On the basis of electrophysiologic properties and histopathology, CMT has been divided into primary peripheral demyelinating (type 1) and primary peripheral axonal (type 2) neuropathies. The demyelinating neuropathies classified as CMT type 1, also known as HMSN I, are characterized by severely reduced motor nerve conduction velocities (NCV) (less than 38 m/s) and segmental demyelination and remyelination with onion bulb formations on nerve biopsy (see CMT1B; 118200). The axonal neuropathies classified as CMT type 2, also known as HMSN II, are characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy (see CMT2A1; 118210). Distal hereditary motor neuropathy (dHMN) (see 158590) is a spinal type of CMT characterized by exclusive motor involvement and sparing of sensory nerves (Pareyson, 1999). There are X-linked, autosomal dominant (see 118200), and autosomal recessive (see 214400) forms of CMT.

The form of Charcot-Marie-Tooth neuropathy that maps to chromosome Xq13 (CMTX1) is X-linked dominant or X-linked intermediate; heterozygous females are more mildly affected than are hemizygous males."

PMID: 20301548/GeneReviews: "Peripheral neuropathy typically manifests in affected males between ages five and 25 years. Although both men and women are affected, manifestations tend to be less severe in women, some of whom
may remain asymptomatic"

Created: 13 Dec 2024, 5:04 a.m. | Last Modified: 13 Dec 2024, 5:04 a.m.

Panel Version: 1.825

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM#302800

Publications

• 20301548

Green List (high evidence)

Childhood onset, motor disability can be severe.

Created: 9 Sep 2022, 5:47 a.m. | Last Modified: 9 Sep 2022, 5:47 a.m.

Panel Version: 0.185

All isolated neuropathies should be treated the same. Explore further before making a decision.

Created: 18 Aug 2022, 6:49 a.m. | Last Modified: 18 Aug 2022, 6:49 a.m.

Panel Version: 0.151

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM# 302800

I don't know

CMTX has both demyelinating and axonal features. Well established gene-disease association, over 100 families reported. Variable phenotype with incomplete penetrance (OMIM)

PMID 31842800: Three unrelated males with GJB1 variants and recurrent episodes of reversible posterior leukoencephalopathy reported.
Sources: Literature

Created: 25 Jul 2022, 1:17 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Charcot-Marie-Tooth neuropathy, X-linked dominant, 1 (MIM#302800)