TY - JOUR
T1 - DNA Rearrangements on both homologues of chromosome 17 in a mildly delayed individual with a family history of autosomal dominant carpal tunnel syndrome
AU - Potocki, Lorraine
AU - Chen, Ken Shiung
AU - Koeuth, Thearith
AU - Killian, James
AU - Iannaccone, Susan T.
AU - Shapira, Stuart K.
AU - Kashork, Catherine D.
AU - Spikes, Aimee S.
AU - Shaffer, Lisa G.
AU - Lupski, James R.
N1 - Funding Information:
We thank this family, for participating in our research, and Doreen Osterholm, who provided invaluable technical assistance. This research was supported, in part, by grants from the National Institute of Child Health and Development (NIH) (K08HD01149) (to L.P.), the National Institute of Neurological Disorders and Strokes (NIH) (R01NS2742) (to J.R.L.), the Muscular Dystrophy Association of America (to J.R.L), the Baylor Mental Retardation Research Center (HD2406402), the Child Health Research Center (HD94021), and the Texas Children's Hospital General Clinical Research Center (M01RR00188).
PY - 1999
Y1 - 1999
N2 - Disorders known to be caused by molecular and cytogenetic abnormalities of the proximal short arm of chromosome 17 include Charcot-Marie-Tooth disease type 1A (CMT1A), hereditary neuropathy with liability to pressure palsies (HNPP), Smith-Magenis syndrome (SMS), and mental retardation and congenital anomalies associated with partial duplication of 17p. We identified a patient with multifocal mononeuropathies and mild distal neuropathy, growth hormone deficiency, and mild mental retardation who was found to have a duplication of the SMS region of 17p11.2 and a deletion of the peripheral myelin protein 22 (PMP22) gene within 17p12 on the homologous chromosome. Further molecular analyses reveal that the dup(17)(p11.2p11.2) is a de novo event but that the PMP22 deletion is familial. The family members with deletions of PMP22 have abnormalities indicative of carpal tunnel syndrome, documented by electrophysiological studies prior to molecular analysis. The chromosomal duplication was shown by interphase FISH analysis to be a tandem duplication. These data indicate that familial entrapment neuropathies, such as carpal tunnel syndrome and focal ulnar neuropathy syndrome, can occur because of deletions of the PMP22 gene. The co-occurrence of the 17p11.2 duplication and the PMP22 deletion in this patient likely reflects the relatively high frequency at which these abnormalities arise and the underlying molecular characteristics of the genome in this region.
AB - Disorders known to be caused by molecular and cytogenetic abnormalities of the proximal short arm of chromosome 17 include Charcot-Marie-Tooth disease type 1A (CMT1A), hereditary neuropathy with liability to pressure palsies (HNPP), Smith-Magenis syndrome (SMS), and mental retardation and congenital anomalies associated with partial duplication of 17p. We identified a patient with multifocal mononeuropathies and mild distal neuropathy, growth hormone deficiency, and mild mental retardation who was found to have a duplication of the SMS region of 17p11.2 and a deletion of the peripheral myelin protein 22 (PMP22) gene within 17p12 on the homologous chromosome. Further molecular analyses reveal that the dup(17)(p11.2p11.2) is a de novo event but that the PMP22 deletion is familial. The family members with deletions of PMP22 have abnormalities indicative of carpal tunnel syndrome, documented by electrophysiological studies prior to molecular analysis. The chromosomal duplication was shown by interphase FISH analysis to be a tandem duplication. These data indicate that familial entrapment neuropathies, such as carpal tunnel syndrome and focal ulnar neuropathy syndrome, can occur because of deletions of the PMP22 gene. The co-occurrence of the 17p11.2 duplication and the PMP22 deletion in this patient likely reflects the relatively high frequency at which these abnormalities arise and the underlying molecular characteristics of the genome in this region.
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U2 - 10.1086/302240
DO - 10.1086/302240
M3 - Article
C2 - 9973284
AN - SCOPUS:0033072223
SN - 0002-9297
VL - 64
SP - 471
EP - 478
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -