Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a). The HMSN Collaborative Research Group.
Hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT 1) is an autosomal dominant disorder of the peripheral nervous system characterized by progressive weakness and atrophy of distal limb muscles. In the majority of HMSN I families, linkage studies localized the gene (CMT 1a) to the pericentromeric region of chromosome 17. We have detected with probe pVAW409R3 (D17S122) localized in 17p11.2 a duplication, co-segregating with the disease in 12 HMSN I families. In these families the duplication was present in all 128 patients but absent in the 84 unaffected and 44 married-in individuals (lod score of 58.44 at zero recombination). Further, on one HMSN I family the disease newly appeared simultaneously with a de novo duplication originating from an unequal crossing-over event at meiosis. Since different allelic combinations were found segregating with the duplication in different families linkage disequilibrium was not a significant factor. These findings led us to propose that the duplication in 17p11.2 itself is the disease causing mutation in all the HMSN I families analyzed.
Raeymaekers
P
P
Born-Bunge Foundation, Department of Biochemistry, University of Antwerp (UIA), Belgium.
Timmerman
V
V
Nelis
E
E
De Jonghe
P
P
Hoogendijk
J E
JE
Baas
F
F
Barker
D F
DF
Martin
J J
JJ
De Visser
M
M
Bolhuis
P A
PA
D001345:Autoradiography; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004247:DNA / Q000737:chemistry; D015342:DNA Probes; D005819:Genetic Markers; D015894:Genome, Human; D006801:Humans; D011110:Polymorphism, Genetic
D015342:DNA Probes; D005819:Genetic Markers; D004247:DNA