Bloom's syndrome: Clinical spectrum, molecular pathogenesis, and cancer predisposition

Christopher M Cunniff, Jennifer A. Bassetti, Nathan Ellis

Research output: Contribution to journalReview article

37 Citations (Scopus)

Abstract

Bloom's syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early onset of cancer and for the development of multiple cancers. Loss-of-function mutations of BLM, which codes for a RecQ helicase, cause Bloom's syndrome. The absence of a functional BLM protein causes chromosome instability, excessive homologous recombination, and a greatly increased number of sister chromatid exchanges that are pathognomonic of the syndrome. A common founder mutation designated blmAsh is present in about 1 in 100 persons of Eastern European Jewish ancestry, and there are additional recurrent founder mutations among other populations. Missense, nonsense, and frameshift mutations as well as multiexonic deletions have all been observed. Bloom's syndrome is a prototypical chromosomal instability syndrome, and the somatic mutations that occur as a result of that instability are responsible for the increased cancer risk. Although there is currently no treatment aimed at the underlying genetic abnormality, persons with Bloom's syndrome benefit from sun protection, aggressive treatment of infections, surveillance for insulin resistance, and early identification of cancer.

Original languageEnglish (US)
Pages (from-to)4-23
Number of pages20
JournalMolecular Syndromology
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Bloom Syndrome
Chromosomal Instability
Mutation
Insulin Resistance
Neoplasms
RecQ Helicases
Frameshift Mutation
Sister Chromatid Exchange
Nonsense Codon
Homologous Recombination
Solar System
Missense Mutation
Skin
Therapeutics
Growth
Infection
Population

Keywords

  • BLM
  • Bloom's syndrome
  • Cancer

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Bloom's syndrome : Clinical spectrum, molecular pathogenesis, and cancer predisposition. / Cunniff, Christopher M; Bassetti, Jennifer A.; Ellis, Nathan.

In: Molecular Syndromology, Vol. 8, No. 1, 01.01.2017, p. 4-23.

Research output: Contribution to journalReview article

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