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HNPP Associated With An Alternatively‐Sized Deletion At Chromosome 17p11.2‐p12
Author(s) -
Taioli F,
Fabrizi GM,
Rigatelli F,
Rizzuto N.
Publication year - 2001
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2001.01007-48.x
Subject(s) - biology , genetics , gene duplication , loss of heterozygosity , chromosome , gene , compound heterozygosity , mutation , deletion mapping , microbiology and biotechnology , allele
Chromosome 17p11.2‐p12 is prone to unequal crossing‐over events associated with inherited neuropathies (17p12) and with forms of mental retardation known as Smith Magenis Syndrome (SMS) (17p11.2). A 1.5 megabase (Mb) duplication or deletion encompassing the PMP22 gene causes respectively Charcot‐Marie‐Tooth neuropathy type 1A (CMT1A) and Hereditary Neuropathy with liability to Pressure Palsies (HNPP); the unequal crossing over is caused by misalignment of two low‐copy repeat elements named CMT1A‐REP which flank the duplicated/deleted region. HNPP is genetically homogenous; only exceptional cases have been associated with non‐sense mutations of PMP22. In a four‐generation pedigree five individuals were affected with a clinically and pathologically typical HNPP (tomaculous neuropathy). PFGE analysis with SacII endonuclease and probe pNEA101, which maps to the proximal CMT1A‐REP, failed to detect the 770 and 820 kb junction fragments associated with the 1.5‐Mb deletion. Restriction by SacII and NotI showed respectively two novel junction fragments of ≅1.1 and 1.25 Mb, suggesting the presence of a shorter deletion. Nucleotide sequencing of PMP22 was normal. Linkage analysis using the markers D17S1921, D17S839, D17S1357, D17S12, D17S261, D17S953 and D17S1843 confirmed the results of PFGE by demonstrating loss of heterozygosity for D17S1357 and D17S122. The report underlines the high instability of chromosome 17p11.2‐p12 and prompts to investigate other mechanisms of genetic rearrangement in that region.