title: Next generation sequencing in the identification of a rare genetic disease from preconceptional couple screening to preimplantation genetic diagnosis.
abstract: BACKGROUND
  the use of Next Generation Sequencing (NGS) in the diagnosis of rare genetic pathologies is becoming ever more widespread in clinical practice. The following study reports the first case of preimplantation diagnosis through NGS of a form of LAMA2-related muscular dystrophy.
  
  
  METHODS
  a couple came to our Reproductive Medicine Centre for a preconceptional genetic consultation and for advice regarding secondary infertility. The couple already had a 3-year-old child who was suffering from a form of muscular dystrophy that has yet to be genetically defined. The disease had been diagnosed at the age of 6 months. A blood sample was taken from both parents and the child in order to analyze the DNA through the Illumina NextSeq 500 platform and an enrichment protocol, Trusight One Sequencing Panel, created by Illumina for the simultaneous sequencing of the exon regions of 4,813 clinically relevant genes. This led to the identification of 2 point mutations in the LAMA2 gene, each inherited by a parent. The couple then underwent a cycle of IVF (in vitro fertilization). A preimplantation genetic diagnosis was carried out on the embryos obtained after setting up a protocol for the analysis of a point mutation in the LAMA2 gene, (this mutation has yet to be described in literature) and the normal embryos together with the recessive LAMA2-related muscular dystrophy related carriers were transferred. There were no complications during pregnancy, which terminated with a cesarean section at 39 weeks and the birth of healthy 3430-gram baby.
  
  
  CONCLUSIONS
  given its robustness, reliability and reproducibility, NGS could also be useful in prenatal diagnosis. This technique could guarantee an ample and quick analysis of the genes involved in development, making it possible to organize medical interventions during pregnancy and after birth.
authors.affiliation: Department of Genetics, Altamedica-Artemisia SpA, Rome.
authors.forename: Claudio
authors.initials: C
authors.lastname: Dello Russo
authors.affiliation: Department of Genetics, Altamedica-Artemisia SpA, Rome.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Di Giacomo
authors.affiliation: Department of Genetics, Altamedica-Artemisia SpA, Rome.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mesoraca
authors.affiliation: Department of Fetal Maternal Medicine, Altamedica-Artemisia SpA, Rome.
authors.forename: Laura
authors.initials: L
authors.lastname: D'Emidio
authors.affiliation: Department of Reproductive Medicine, Altamedica-Artemisia SpA, Rome.
authors.forename: Paola
authors.initials: P
authors.lastname: Iaconianni
authors.affiliation: Department of Reproductive Medicine, Altamedica-Artemisia SpA, Rome.
authors.forename: Elisa
authors.initials: E
authors.lastname: Minutolo
authors.affiliation: Department of Reproductive Medicine, Altamedica-Artemisia SpA, Rome.
authors.forename: Assunta
authors.initials: A
authors.lastname: Lippa
authors.affiliation: Department of Fetal Maternal Medicine, Altamedica-Artemisia SpA, Rome.
authors.forename: Claudio
authors.initials: C
authors.lastname: Giorlandino
keywords: Lama2 related muscular dystrophy; Next Generation Sequencing; preimplantation genetic diagnosis