PMID- 17286450
OWN - NLM
STAT- MEDLINE
DCOM- 20070423
LR  - 20181113
IS  - 1177-1062 (Print)
IS  - 1177-1062 (Linking)
VI  - 11
IP  - 1
DP  - 2007
TI  - RB1 germ-line deletions in Argentine retinoblastoma patients.
PG  - 55-61
AB  - BACKGROUND: Retinoblastoma (RB) is a malignant tumor originating in the retinal 
      cell precursors and can be presented as a unilateral or bilateral form in 
      childhood (one or both eyes affected). Development of this tumor is caused by 
      mutations in the RB1 gene on chromosome 13q14; the first mutation may occur in 
      the germ line (hereditary RB) or in somatic cells (non-hereditary RB). The 
      hereditary form of RB is transmitted with a high penetrance to offspring (90%). 
      Because early diagnosis is necessary for implementing effective treatment and 
      preserving vision, it is important to identify the mutations in the affected 
      family. AIM: The aim of this study was to identify large and small RB1 germ-line 
      mutations and to correlate them with the RB phenotype. METHODS: Constitutional 
      RB1 gene gross deletions were studied in 40 patients with bilateral or unilateral 
      familial RB by a segregation assay of four intragenic polymorphisms located in 
      introns 1, 4, 17, and 20 of the RB1 gene, along with fluorescence in situ 
      hibridization (FISH) analysis. Small mutations were ascertained in a subgroup of 
      ten patients by heteroduplex/sequence analysis of RB1-exons. RESULTS: In the 
      course of our study, we have found three large deletions, which probably 
      represent whole gene deletions, and two small deletions of 1bp in length. One 
      large deletion was found in a family with several members affected. This 
      represents a rare case of familial RB, which is usually caused by small 
      mutations. Phenotype analysis of the family revealed a low penetrance 
      inheritance, with an 'affected eyes : number of mutation-carriers' ratio of 
      approximately 1.0, whereas this ratio in families with small loss-of-function 
      mutations is 1.5-2.0. CONCLUSIONS: Our results emphasize the usefulness of a 
      combined methodology that includes segregation of polymorphisms, FISH, and 
      heteroduplex/sequence analyses for detection of gross and small DNA 
      rearrangements in familial and sporadic RB. Identification of mutations in 
      sporadic cases is important for risk-assessment in patients' relatives. The 
      degree of penetrance in the inheritance of RB not only depends on the occurrence 
      of the second mutation in the RB1 gene but also on the extent of inactivation of 
      the first mutation.
FAU - Fernandez, Cecilia
AU  - Fernandez C
AD  - Genetics and Molecular Biology Department, Faculty of Pharmacy, Jose de San 
      Martin Hospital, Buenos Aires University, Buenos Aires, Argentina.
FAU - Repetto, Karina
AU  - Repetto K
FAU - Dalamon, Viviana
AU  - Dalamon V
FAU - Bergonzi, Fenanda
AU  - Bergonzi F
FAU - Ferreiro, Veronica
AU  - Ferreiro V
FAU - Szijan, Irene
AU  - Szijan I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Mol Diagn Ther
JT  - Molecular diagnosis & therapy
JID - 101264260
RN  - 0 (Retinoblastoma Protein)
SB  - IM
MH  - Argentina
MH  - Chromosomes, Human, Pair 13
MH  - Exons
MH  - Eye Neoplasms/*genetics
MH  - Functional Laterality
MH  - *Gene Deletion
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Minisatellite Repeats
MH  - Retinoblastoma/*genetics
MH  - Retinoblastoma Protein/*genetics
EDAT- 2007/02/09 09:00
MHDA- 2007/04/24 09:00
CRDT- 2007/02/09 09:00
PHST- 2007/02/09 09:00 [pubmed]
PHST- 2007/04/24 09:00 [medline]
PHST- 2007/02/09 09:00 [entrez]
AID - 1115 [pii]
AID - 10.1007/BF03256222 [doi]
PST - ppublish
SO  - Mol Diagn Ther. 2007;11(1):55-61. doi: 10.1007/BF03256222.