Distal hereditary motor neuropathy type II (distal HMN type II): phenotype and molecular genetics.
The distal hereditary motor neuropathies (distal HMN) are clinically and genetically heterogeneous and are subdivided in seven subtypes according to the mode of inheritance, age at onset and clinical evolution. We studied a multigenerational Belgian pedigree with autosomal dominant distal HMN type II. The clinical phenotype closely resembles classical Charcot-Marie-Tooth (CMT) disease with an age at onset between 15 and 25 years. Linkage studies have shown that distal HMN II is not linked to the known CMT1 and CMT2 loci. A genome-wide search was performed and significant linkage was obtained between markers D12S86 and D12S340, suggesting that a gene causing distal HMN II is located on chromosome 12q24.3. The gene encoding the human pancreatic phospholipase A2 (PLA2A), which is expressed in peripheral nerves during degeneration, is a positional candidate gene. Because no disease-specific mutations were detected in the coding region, however, PLA2A is most likely not the disease causing gene. A yeast artificial chromosome (YAC) contig map spanning the candidate region has been constructed to isolate the gene responsible for distal HMN II. Positional and functional candidate genes are currently being screened for the presence of mutations in distal HMN II patients.
Timmerman
V
V
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), Antwerpen, Belgium. timmerm@uia.ua.ac.bc
Beuten
J
J
Irobi
J
J
De Jonghe
P
P
Martin
J J
JJ
Van Broeckhoven
C
C
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001530:Belgium; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000201:enzymology; D010375:Pedigree; D010641:Phenotype; D010741:Phospholipases A / Q000235:genetics*; D054467:Phospholipases A2
D010741:Phospholipases A; D054467:Phospholipases A2