Molecular and prenatal diagnosis in retinoblastoma affected family: findings from Next-Generation Sequencing

Backgrounds: Retinoblastoma (RB) is a malignant tumor that usually develops in earlychildhood, usually before age five years. This form of cancer develops in the retina, which is thespecialized light-sensitive tissue at the back of the eye that detects light and color. This diseasedevelops from cells that have cancer-predisposing compound heterozygous or homozygousvariants in the retinoblastoma gene (RB۱). Heritable RB is an autosomal dominant disease withhigh penetrance. Individuals with heritable RB are also at increased risk of developing nonoculartumors.Materials and Methods: Whole exome sequencing (WES) was performed for detection ofdisease-causing mutation at peripheral blood in RB affected family's proband. Prenatal diagnosis(PND) was also performed for the family's next pregnancy.Results: The molecular analysis of the affected family showed the c.۱۹۶۰G>C (p.Val۶۵۴Leu)likely pathogenic mutation in exon ۱۹ of the RB۱ (NM_۰۰۰۳۲۱.۳) gene in the affected boy withbilateral retinoblastoma. PND test revealed no mutation in the fetus.Conclusion: Retinoblastoma as a highly malignant intraocular tumor requiring an earlydiagnosis and immediate treatment. Mutations in the RB۱ gene are responsible for most casesand genetic screening of retinoblastoma patients and relatives is important for preciseclassification, efficient treatment or management and genetic counseling purposes. In addition,RB۱ gene mutation studies may help decipher the molecular mechanisms leading to tumors withdifferent degrees of penetrance or expressivity. Today use of next-generation sequencing (NGS)methods as efficient and comprehensive approaches was demonstrated for the identification of awide spectrum of pathogenic variants in RB patients.

کلیدواژه ها:

Retinoblastoma ، Next generation sequencing ، Whole exome sequencing ، Molecular diagnosis ، Prenatal diagnosis