DNA rearrangements affecting dosage sensitive genes

Lawrence Reiter, Tatsufumi Murakami, Laura E. Warner, James R. Lupski

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are two dominantly inherited disorders affecting the peripheral nervous system. The relationship between these two disorders is unique among related syndromes. The tandem duplication of a 1.5 Mb region located on chromosome 17 (17p11.2-p12), which contains the peripheral myelin protein gene PMP22, results in a CMT1A phenotype, whereas the reciprocal deletion of this 1.5 Mb region yields an HNPP phenotype. Therefore, CMT1A duplication patients are triploid for this region of chromosome 17, and HNPP deletion patients are haploid. The genetic mechanism that generates the phenotypic features in aneuploid mental retardation syndromes like Down syndrome (trisomy 21) and Miller-Dieker syndrome (del 17p13) may prove to be similar to the PMP22 gene dosage effects, which result in CMT1A and HNPP. Studying the relationship between the phenotypic features and the underlying mechanism of these two neuropathies may elucidate unique features of neuronal genes that predispose them to dosage sensitivity.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalMental Retardation and Developmental Disabilities Research Reviews
Volume2
Issue number3
StatePublished - Dec 1 1996
Externally publishedYes

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Charcot-Marie-Tooth Disease
Gene Dosage
Gene Rearrangement
Down Syndrome
Classical Lissencephalies and Subcortical Band Heterotopias
Myelin Proteins
Phenotype
Triploidy
Chromosomes, Human, Pair 17
Haploidy
Aneuploidy
Peripheral Nervous System Diseases
Intellectual Disability
Genes

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Neuropsychology and Physiological Psychology
  • Genetics(clinical)

Cite this

DNA rearrangements affecting dosage sensitive genes. / Reiter, Lawrence; Murakami, Tatsufumi; Warner, Laura E.; Lupski, James R.

In: Mental Retardation and Developmental Disabilities Research Reviews, Vol. 2, No. 3, 01.12.1996, p. 139-146.

Research output: Contribution to journalArticle

Reiter, Lawrence ; Murakami, Tatsufumi ; Warner, Laura E. ; Lupski, James R. / DNA rearrangements affecting dosage sensitive genes. In: Mental Retardation and Developmental Disabilities Research Reviews. 1996 ; Vol. 2, No. 3. pp. 139-146.
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