TY  - CHAP
M1  - Book, Section
TI  - Bloom Syndrome
A1  - German, James
A1  - Ellis, Nathan A.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/ommbid.331
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Clinically,  Bloom  syndrome  (BS)  features  (a)  proportional  dwarfism,  usually  accompanied  by  (b)  a  sun-sensitive  erythematous  skin  lesion  limited  to  the  face  and  dorsa  of  the  hands  and  forearms,  (c)  a  characteristic  facies  and  head  configuration,  and  (d)  immunodeficiency,  often  associated  with  otitis  media  and  pneumonia.  (e)  Affected  males  fail  to  produce  spermatozoa,  and  females  although  sometimes  fertile  experience  an  unusually  early  cessation  of  menstrual  cycles.  (f)  Excessive  numbers  of  well-circumscribed  areas  of  dermal  hypo-  and  hyperpigmentation  are  present.  (g)  The  three  major  complications  are  chronic  lung  disease,  diabetes  mellitus,  and—by  far  the  most  important  and  most  frequent—cancer.BS  is  a  genetically  determined  trait  that  is  transmitted  in  a  straightforward  autosomal  recessive  fashion,  with  mutations  at  a  single  locus,  BLM,  being  responsible.  Various  mutations  at  BLM  are  segregating  in  human  populations,  but  the  same  phenotype  (BS)  is  produced  by  either  homozygosity  or  compound  heterozygosity  of  those  so  far  identified.  The  mutations  are  predominantly  null  alleles,  but  missense  mutations  also  have  been  detected.  BS  is  rare  in  all  populations,  but  in  the  Ashkenazi  Jewish  population,  one  particular  mutant  allele,  a  6-bp  deletion  and  7-bp  insertion  that  results  in  premature  translation  termination,  has,  through  founder  effect,  reached  a  relatively  high  carrier  frequency  of  approximately  1  percent;  in  31  percent  of  all  persons  with  BS,  one  or  both  parents  are  Ashkenazi  Jews.The  genome  is  abnormally  unstable  in  the  somatic  cells  of  persons  with  BS.  Mutations  arise  spontaneously  and  accumulate  in  numbers  manyfold  greater  than  normal,  including  both  microscopically  visible  chromatid  gaps,  breaks,  and  rearrangements  and  mutations  at  specific  loci.  Exchanges  take  place  excessively  between  chromatids,  usually  at  what  appear  to  be  homologous  sites.  One  consequence  of  this  hyperrecombinability  is  the  reduction  to  homozygosity  of  constitutionally  heterozygous  loci  distal  to  the  points  of  crossing-over.  The  hyperrecombinability  in  persons  with  BS  who  are  genetic  compounds  can  lead  to  reversion  at  BLM  itself:  Crossing-over  between  two  different  mutated  sites  within  BLM  can  result  in  the  generation  of  a  functionally  normal  gene,  and  thereby  correction  of  the  cellular  phenotype  of  the  somatic  cells  that  comprise  the  progeny  of  the  cell  in  which  the  recombinational  event  had  occurred.Many  of  the  clinical  characteristics  of  BS  may  be  viewed  as  direct  or  indirect  consequences  of  the  hypermutability.  It  is  postulated  to  be  a  major  causative  factor  in  BS's  small  size  by  way  of  the  induction  of  factors  which  either  inhibit  further  cell  division  or  promote  cell  death.  Another  major  consequence  of  the  hypermutability  is  proneness  to  neoplasia;  BS  more  than  any  other  known  human  state  predisposes  to  the  development  of  cancer  of  the  types  and  sites  that  affect  the  general  population,  and  at  unusually  early  ages.  BS  thus  is  the  prototype  of  a  class  of  disease  that  may  be  called  the  somatic  mutational  disorders.Diagnosis  of  BS  is  based  on  clinical  observation;  the  phenotype  is  striking.  Laboratory  confirmation  ordinarily  is  by  cytogenetic  demonstration  of  the  characteristically  increased  tendency  of  chromatid  exchange  to  take  place.  BS  is  the  only  condition  known  that  features  a  greatly  increased  rate  of  sister-chromatid  exchange  (SCE).  Blood  lymphocytes  in  short-term  culture  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/ommbid.331
Y2  - 2024/04/20
UR  - ommbid.mhmedical.com/content.aspx?aid=1181414248
ER  -