Type 2C Research Update

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Abstract from Neurology 2003 Apr 8;60(7):1151-6

The gene for HMSN2C maps to 12q23-24: a region of neuromuscular

disorders.

Klein CJ, Cunningham JM, Atkinson EJ, Schaid DJ, Hebbring SJ,

SA, Klein DM, Dyck PJ, Litchy WJ, Thibodeau SN, Dyck PJ.

Peripheral Neuropathy Research Laboratory, Mayo Clinic

and Mayo Foundation, Rochester, MN, USA.

BACKGROUND: Hereditary motor and sensory neuropathy type 2C (HMSN2C,

Charcot Marie Tooth 2C [CMT2C]) is an autosomal dominant motor and

sensory neuropathy involving limb, diaphragm, vocal cord, and

intercostal muscles.

OBJECTIVE: To identify the chromosome localization for this disorder in

one large American family of English and ish ethnicity.

METHODS: Variable clinical severity led the authors to combine several

approaches to accurately identify affected patients. Genome-wide

two-point linkage analysis, high-definition mapping, and multipoint and

recombinant haplotype analyses were performed. Mutation analysis of the

triplet repeat region of ataxin-2 was also carried out.

RESULTS: The initial genome-wide scan identified a region at 12q24, and

fine mapping provided a maximal lod score of 4.73 (D12S1645 and D12S1583

at theta = 0.01 and 0,

respectively). With multipoint analysis, a higher lod score of 5.17 was

obtained and localized to the same region at 119.0 cM. Haplotype

analysis narrowed the region to approximately 5.0 cM between

D12S1646,D12S1330 and D12S105,D12S1339 (12q23.3-24.21). Ataxin-2, the

gene responsible for spinocerebellar ataxia type 2 (SCA2), localizes to

this region, but no triplet repeat expansion or point mutations within

the repeat

were found.

CONCLUSIONS: The gene for HMSN2C maps to 12q23-24. This region is

associated with SCA2, scapuloperoneal spinal muscular atrophy, and

congenital distal spinal muscular atrophy. Further studies are needed to

demonstrate the specific gene alteration and its relationship with

nearby genes.