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Mariana V Salles, Fabiana Louise Motta, Karita Antunes Costa, John Chiang, João Bosco Pesquero, Juliana M F Sallum; Segregation analyze in Stargardt patients’ families: investigation of complex allele in ABCA4 gene. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2775.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate occurrence of two mutations in the same chromosome in ABCA4 gene in Brazilian patients with diagnosis of Stargardt disease
The ABCA4 gene was first sequenced with next generation technique in the Stargardt patients. For the conclusion of the molecular tests, segregation analyze is useful to determinate the family inheritance of each pathogenic variation. Among a group of 23 families, 10 families were selected for segregation analysis to study the possibility of complex alleles. As inclusion criteria the proband must have three pathogenic variations or two variations suspect to be at a single chromosome (complex allele). The Sanger sequencing technique was used for segregation analysis. The molecular results were compared with available databases. Besides the genetic evaluation, the clinical characteristics of the patients were evaluated
Those 10 families underwent the segregation analysis and it was able to confirm the presence of three different complex allele in ABCA4 gene. They were: [p.Leu541Pro and p.Arg1443His] in three families; [p.Leu541Pro and p.Ala1038Val] in one family and [p.Ser1642Arg and c.5044_del15bp] in six families. The [p.Leu541Pro and p.Ala1038Val] was already known but the other two are new (Fig.1). Stargardt disease is autosomal recessive when caused by variations in ABCA4 gene. The molecular diagnoses can be conclusive if with the complex allele the patient also has another pathogenic variation in the other chromosome. In addition to that new information, the molecular tests identify 2 new variations as the second allele in ABCA4 gene
The segregation analysis was important to confirm the molecular diagnosis of patients with Stargardt disease due to the possible presence of more them two pathogenic variations in the ABCA4 gene. The knowledge about variations in the same chromosome can help to determinate the molecular diagnose. The identification of these two new complex allele, [p.Leu541Pro; p.Arg1443His] and [p.Ser1642Arg; c.5044_del15bp] in Brazilian alert for the possibility of more different variations in cis
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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