Friederike Ehrhart1,2, Nasim B Sangani1,2, Leopold M G Curfs1,2. 1. Rett Expertise Centre - GKC, Maastricht University Medical Centre. 2. Department of Bioinformatics, Maastricht University, The Netherlands.
Abstract
PURPOSE OF REVIEW: This article reviews the current molecular genetic studies, which investigate the genetic causes of Rett syndrome or Rett-like phenotypes without a MECP2 mutation. RECENT FINDINGS: As next generation sequencing becomes broadly available, especially whole exome sequencing is used in clinical diagnosis of the genetic causes of a wide spectrum of intellectual disability, autism, and encephalopathies. Patients who were diagnosed with Rett syndrome or Rett-like syndrome because of their phenotype but were negative for mutations in the MECP2, CDKL5 or FOXG1 genes were subjected to whole exome sequencing and the results of the last few years revealed yet 69 different genes. Many of these genes are involved in epigenetic gene regulation, chromatin shaping, neurotransmitter action or RNA transcription/translation. Genetic data also allows to investigate the individual genetic background of an individual patient, which can modify the severity of a genetic disorder. SUMMARY: We conclude that the Rett syndrome phenotype has a much broader underlying genetic cause and the typical phenotype overlap with other genetic disorders. For proper genetic counselling, patient perspective and treatment it is important to include both phenotype and genetic information.
PURPOSE OF REVIEW: This article reviews the current molecular genetic studies, which investigate the genetic causes of Rett syndrome or Rett-like phenotypes without a MECP2 mutation. RECENT FINDINGS: As next generation sequencing becomes broadly available, especially whole exome sequencing is used in clinical diagnosis of the genetic causes of a wide spectrum of intellectual disability, autism, and encephalopathies. Patients who were diagnosed with Rett syndrome or Rett-like syndrome because of their phenotype but were negative for mutations in the MECP2, CDKL5 or FOXG1 genes were subjected to whole exome sequencing and the results of the last few years revealed yet 69 different genes. Many of these genes are involved in epigenetic gene regulation, chromatin shaping, neurotransmitter action or RNA transcription/translation. Genetic data also allows to investigate the individual genetic background of an individual patient, which can modify the severity of a genetic disorder. SUMMARY: We conclude that the Rett syndrome phenotype has a much broader underlying genetic cause and the typical phenotype overlap with other genetic disorders. For proper genetic counselling, patient perspective and treatment it is important to include both phenotype and genetic information.
Authors: Amit L Deshmukh; Antonio Porro; Mohiuddin Mohiuddin; Stella Lanni; Gagan B Panigrahi; Marie-Christine Caron; Jean-Yves Masson; Alessandro A Sartori; Christopher E Pearson Journal: J Huntingtons Dis Date: 2021
Authors: Mari Wold Henriksen; Kirstine Ravn; Benedicte Paus; Stephen von Tetzchner; Ola H Skjeldal Journal: BMC Med Genet Date: 2018-10-11 Impact factor: 2.103