Application of next generation sequencing in genetic counseling a case of a couple at risk of cystinosis

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RESEARCH ARTICLE

Open Access

Application of next generation sequencing in genetic counseling a case of a couple at risk of cystinosis Mouna Ouhenach1,2* , Abdelali Zrhidri1,2, Imane Cherkaoui Jaouad1,2, Wiam Smaili1 and Abdelaziz Sefiani1,2

Abstract Background: In Morocco, consanguinity rate is very high; which lead to an increase in the birth prevalence of infants with autosomal recessive disorders. Previously, it was difficult to diagnose rare autosomal recessive diseases. Next Generation Sequencing (NGS) techniques have considerably improved clinical diagnostics. A genetic diagnosis showing biallelic causative mutations is the requirement for targeted carrier testing in parents, prenatal and preimplantation genetic diagnosis in further pregnancies, and also for targeted premarital testing in future couples at risk of producing affected children by a known autosomal recessive disease. Methods: In this report, we present our strategy to advise a future couple of first cousins, whose descendants would risk cystinosis; an autosomal recessive lysosomal disease caused by mutations in the CTNS gene. Indeed, our future husband’s sister is clinically and biochemically diagnosed with cystinosis in early childhood. First, we opted to identify the patient’s CTNS gene abnormality by using (NGS), then we searched for heterozygosity in the couple’s DNA, which allows us to predict the exact risk of this familial disease in the future couple’s offspring. Results: We have shown that the future husband, brother of the patient is heterozygous for the familial mutation. On the other hand, his future wife did not inherit the familial mutation. Therefore, genetic counseling was reassuring for the risk of familial cystinosis in this couple’s offspring. Conclusions: We report in this study, one of the major applications of (NGS), an effective tool to improve clinical diagnosis and to provide the possibility of targeted premarital carrier testing in couples at risk. Keywords: Next generation sequencing, Consanguinity, Genetic counseling, Cystinosis

Background Morocco is one of the countries with a high rate of consanguinity in the Mediterranean, where consanguineous marriages account for 15.25% of all marriages, and 58.46% of them are between first cousins [1]. Autosomal recessive disorders are strongly associated with consanguineous marriages; the frequency of these marriages are estimated

* Correspondence: [email protected] 1 Department of Medical Genetics, National Institute of Health, 27, Avenue Ibn Battouta, BP 769, Rabat, Morocco 2 Human Genomics Center, Faculty of Medicine and Pharmacy, Rabat, Morocco

at 59.09% among Moroccan families with autosomal recessive disorders [1]. Previously, the large number of potential genes and the phenotypic variability associated with many known genetic causes, have made the diagnosis of rare autosomal recessive disorders very difficult. In recent years, significant advances are achieved using next generation sequencing (NGS) technology in medical practice especially in the diagnosis of child