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Compound heterozygous deletions of PMP22 causing severe Charcot‐Marie‐Tooth disease of the Dejerine‐Sottas disease phenotype
Author(s) -
AlThihli Khalid,
Rudkin Teresa,
Carson Nancy,
Poulin Chantal,
Melançon Serge,
Der Kaloustian Vazken M.
Publication year - 2008
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32456
Subject(s) - compound heterozygosity , genetics , allele , phenotype , exon , biology , heterozygote advantage , medicine , gene
Dejerine‐Sottas disease (DSD) is a particular phenotype of the Charcot‐Marie‐Tooth (CMT) disease spectrum that is genetically heterogeneous. It represents a severe form of hypertrophic axonal and demyelinating neuropathy. Although it is predominantly inherited as an autosomal recessive condition, autosomal dominant inheritance has also been described. To date, the autosomal recessive forms of DSD are classified into several CMT type 4 (CMT4) subclasses based on allelic heterogeneity. We present a 7‐year‐old boy with a severe form of CMT disease consistent with the autosomal recessive phenotype of DSD. He was found to be a compound heterozygote for mutations in the PMP22 gene resulting in homozygous deletion of exons 2 and 3. The maternally inherited allele was the typical 1.5 Mb deletion involving PMP22 seen with hereditary neuropathy with liability to pressure palsy (HNPP). The paternally inherited allele was a deletion of exons 2 and 3. Both parents presented with a typical clinical picture of HNPP. To our knowledge, this is the first patient reported with large deletions involving both PMP22 alleles. Our patient has also developed severe gastroesophageal reflux disease (GERD), a clinical feature not previously reported with CMT or DSD. The correlation of the phenotype and the molecular defects observed in this patient may set a new subcategory in the classification of DSD. © 2008 Wiley‐Liss, Inc.