Clinical and Molecular Studies in a Family With Probable X-linked Dominant Charcot-Marie-Tooth Disease Involving the Central Nervous System

Hisama, Fuki M.; Lee, Helen H.; Vashlishan, Amy; Tekumalla, Poornima; Russell, David; Auld, Elizabeth; Goldstein, Jonathan

doi:10.1001/archneur.58.11.1891

Cited by 10 publications

(8 citation statements)

References 26 publications

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“…Previously, CMTX patients were reported with white matter lesions in the periventricular area, the parietal white matter, and in the splenium of corpus callosum (6)(7)(8). Among them, only one male case showed scattered white matter lesions that were similar to those in our case (6) (12). Although sequence variants in the GJB1 promoter region were detected in this case, direct DNA sequencing of the GJB1 coding region was normal (12).…”

Section: Discussionsupporting

confidence: 65%

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X-linked Charcot-Marie-Tooth Disease (CMTX) in a Severely Affected Female Patient with Scattered Lesions in Cerebral White Matter

et al. 2007

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Section: Discussionsupporting

confidence: 65%

“…Among them, only one male case showed scattered white matter lesions that were similar to those in our case (6) (12). Although sequence variants in the GJB1 promoter region were detected in this case, direct DNA sequencing of the GJB1 coding region was normal (12).…”

Section: Discussionsupporting

confidence: 60%

X-linked Charcot-Marie-Tooth Disease (CMTX) in a Severely Affected Female Patient with Scattered Lesions in Cerebral White Matter

et al. 2007

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“…Brain MRI was available on BAB8201 in which diffuse hyper‐intensity in the white matter on T2‐weighted images suggestive of hypomyelination, thin corpus callosum and reduced brain volume were detected. Clinical information from the family of BAB8201 with positive family history was published separately (Hisama et al, ).…”

Section: Resultsmentioning

confidence: 99%

Xq22 deletions and correlation with distinct neurological disease traits in females: Further evidence for a contiguous gene syndrome

et al. 2019

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Xq22 deletions that encompass PLP1 (Xq22‐PLP1‐DEL) are notable for variable expressivity of neurological disease traits in females ranging from a mild late‐onset form of spastic paraplegia type 2 (MIM# 312920), sometimes associated with skewed X‐inactivation, to an early‐onset neurological disease trait (EONDT) of severe developmental delay, intellectual disability, and behavioral abnormalities. Size and gene content of Xq22‐PLP1‐DEL vary and were proposed as potential molecular etiologies underlying variable expressivity in carrier females where two smallest regions of overlap (SROs) were suggested to influence disease. We ascertained a cohort of eight unrelated patients harboring Xq22‐PLP1‐DEL and performed high‐density array comparative genomic hybridization and breakpoint‐junction sequencing. Molecular characterization of Xq22‐PLP1‐DEL from 17 cases (eight herein and nine published) revealed an overrepresentation of breakpoints that reside within repeats (11/17, ~65%) and the clustering of ~47% of proximal breakpoints in a genomic instability hotspot with characteristic non‐B DNA density. These findings implicate a potential role for genomic architecture in stimulating the formation of Xq22‐PLP1‐DEL. The correlation of Xq22‐PLP1‐DEL gene content with neurological disease trait in female cases enabled refinement of the associated SROs to a single genomic interval containing six genes. Our data support the hypothesis that genes contiguous to PLP1 contribute to EONDT.

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“…In addition, fixed spasticity, hyperreflexia, dysarthria and ataxia have also been reported. [102, 107, 109, 110] A number of studies have reported MRI imaging abnormalities in CMT1X patients. In most cases, these imaging abnormalities are accompanied by clinical findings, [91, 102, 108, 109] while in at least two case no mention is made of accompanying clinical signs or symptoms [111, 112] Interestingly, two reports [102, 109] describe diffuse involvement of the corticospinal/corticobulbar tracts, suggesting that this tract may represent a selectively vulnerable region; the predominance of findings indicative of corticospinal dysfunction in patients with fixed abnormalities, and the predominance of corticospinal findings in patients with florid acute syndromes (see below) also suggest this possibility.…”

Section: Disease Manifestations Of Gjb1 Mutationsmentioning

confidence: 99%

Gap junctions in inherited human disorders of the central nervous system

Abrams

Scherer

2012

Biochimica et Biophysica Acta (BBA) - Biomembranes

105

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CNS glia and neurons express connexins, the proteins that form gap junctions in vertebrates. We review the connexins expressed by oligodendrocytes and astrocytes, and discuss their proposed physiologic roles. Of the 21 members of the human connexin family, mutations in three are associated with significant central nervous system manifestations. For each, we review the phenotype and discuss possible mechanisms of disease. Mutations in GJB1, the gene for connexin 32 (Cx32) cause the second most common form of Charcot-Marie-Tooth disease (CMT1X). Though the only consistent phenotype in CMT1X patients is a peripheral demyelinating neuropathy, CNS signs and symptoms have been found in some patients with CMT1X. Recessive mutations in GJC2, the gene for Cx47, are one cause of Pelizaeus-Merzbacher-like disease (PMLD), which is characterized by nystagmus within the first 6 months of life, cerebellar ataxia by 4 years, and spasticity by 6 years of age. MRI imaging shows abnormal myelination. A different recessive GJC2 mutation causes a form of hereditary spastic paraparesis, which is a milder phenotype than PMLD. Dominant mutations in GJA1, the gene for Cx43, cause oculodentodigital dysplasia (ODDD), a pleitropic disorder characterized by oculo-facial abnormalities including micropthalmia, microcornia and hypoplastic nares, syndactyly of the fourth to fifth fingers and dental abnormalities. Neurologic manifestations, including spasticity and gait difficulties, are often but not universally seen. Recessive GJA1 mutations cause Hallermann-Streiff syndrome, a disorder showing substantial overlap with ODDD.

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Clinical and Molecular Studies in a Family With Probable X-linked Dominant Charcot-Marie-Tooth Disease Involving the Central Nervous System

Abstract: This family differs from others with hereditary motor and sensory neuropathic diseases by the presence of upper motor neuron signs and additional features. The clinical features and inheritance pattern are consistent with X-linked dominant inheritance or autosomal dominant inheritance.

Cited by 10 publications

References 26 publications

X-linked Charcot-Marie-Tooth Disease (CMTX) in a Severely Affected Female Patient with Scattered Lesions in Cerebral White Matter

X-linked Charcot-Marie-Tooth Disease (CMTX) in a Severely Affected Female Patient with Scattered Lesions in Cerebral White Matter

Xq22 deletions and correlation with distinct neurological disease traits in females: Further evidence for a contiguous gene syndrome

Gap junctions in inherited human disorders of the central nervous system

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