RT Book, Section
A1 Sampson, Julian R.
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181479948
T1 Tuberous Sclerosis
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181479948
RD 2024/04/19
AB Tuberous  sclerosis  is  a  multisystem  hamartomatosis  that  is  transmitted  as  an  autosomal  dominant  trait  with  highly  variable  expression.  Prevalence  among  newborns  is  estimated  to  be  over  1  in  10,000  and  is  not  thought  to  show  significant  geographic  variation.Frequent  manifestations  of  tuberous  sclerosis  include  seizures,  intellectual  handicap,  behavioral  problems,  a  variety  of  skin  lesions,  and  renal  angiomyolipomas  and  cysts.  Cardiac  rhabdomyomas  and  hepatic  angiomas  are  also  common,  but  usually  asymptomatic.  The  lungs  and  endocrine  system  are  less  frequently  involved.  Management  is  directed  toward  the  early  detection  and  treatment  of  important  medical  and  psychological  complications  and  the  provision  of  genetic  counseling.Two  tuberous  sclerosis-determining  genes  have  been  identified  by  positional  cloning  and  are  termed  TSC1  and  TSC2.  A  wide  range  of  inactivating  germ  line  mutations  occur  in  patients  with  tuberous  sclerosis.  Demonstration  of  loss  of  heterozygosity  or  intragenic  mutations  affecting  the  corresponding  wild-type  allele  in  hamartomas  indicates  that  both  genes  function  as  Knudson-type  tumor  suppressors.The  TSC1  and  TSC2  encoded  proteins  hamartin  and  tuberin  are  not  homologous  but  interact  directly  with  one  another  to  form  a  largely  cytosolic  complex.  Their  cellular  roles  are  not  well  understood.The  Eker  rat  is  a  naturally  occurring  model  of  TSC2  inactivation.  Its  recognition  has  facilitated  direct  experimental  confirmation  of  the  tumour  suppressor  properties  of  TSC2.  The  gigas  phenotype  in  Drosophila  results  from  inactivating  mutations  of  a  gene  orthologous  to  TSC2.  Homozygous  gigas  −/−  cells  exhibit  a  phenotype  of  cellular  hypertrophy  and  endoreduplication  of  DNA.