Molecular diagnosis in recessive pediatric neurogenetic disease can help reduce disease recurrence in families

• DOI: 10.1186/s12920-020-0714-1
• Publication Date: 2020-05-13T09:19:35Z
• Authors: Mahmoud Y. Issa; Zinayida Chechlacz; Valentina Stanley; Renee D. George; Jennifer McEvoy-V...; Denice Belandres; Hasnaa M. Elbendary; Khaled R. Gaber; Ahmed Nabil; Mohamed S. Abdel-...; Maha S. Zaki; Joseph G. Gleeson
• Keywords: Human genetics; Medical genetics

The causes for thousands of individually rare recessive diseases have been discovered since the adoption next generation sequencing (NGS). Following molecular diagnosis in older children a family, parents could use this information to opt fetal genotyping subsequent pregnancies, which inform decisions about elective termination pregnancy. NGS diagnostic families has not demonstrated yield benefit pregnancies reduce recurrence. Here we evaluated whether genetic supports reduction recurrence neurogenetic disease. Retrospective study involving with child pediatric brain disease (rPBD) that underwent NGS-based diagnosis. Prenatal testing was offered couples made, help seeking prevent With information, made termination. Pregnancies were carried term assessed health and mother, compared historic risk Between 2010 2016, 1172 presented likely rPBD, 526 received diagnosis, 91 returned clinic 101 84 opted genotyping. Sixty tested negative biallelic mutation fetus, all, except one spontaneous abortion, term, unaffected at follow-up. Of 24 genotyped positive mutation, 16 electively terminated, 8 showed features similar affected sibling(s). Among living offspring deviated from expected 25% observed 12% ([95% CI 0·04 0·20], p = 0·011). Molecular an child, coupled prenatal counselling, allows make informed