Genetic and Psychiatric Molecular Analysis in Speech Delay Syndrome

Session

Medicine and Nursing

Description

The work in is a special genetic case and the goal is to know the type of mutation, the genesis of this hitherto unknown case. This study included a population of 9000 individuals in the northern part of Macedonia. During the family interviews, we came across the case of a boy who had speech impediments, aggressive behavior and small deformities in the size of his nose, ears and face. The 5year-old male had slurred voices, not formulating meaningful words that were unclear. Summary- First EEG and genetic analyzes were done. The case at the age of 2 correctly emphasized words such as nana, grandfather, grandmother, but then lost the words. From the questionnaire, they stated that the grandmother's loud voice created stress in the child and they have been living in another region for 3 years, but the changes are very small in speech. Methods and analyses-From targeted genetic analysis such as massively parallel sequencing (Next Generation Sequencing, NGS) in exons of up to 99% of protein-coding genes (Whole Exome Sequencing, WES) for new sequencing with 6000 sequenc- ers. Bioinformatic analyzes for sequencer mapping of fragments as a reference for variants are processed based on Hg19 versions in the human genome reference. Sequencing and analysis were performed at the accredited reference laboratory - CeGaT GmbH, Tubingen, Germany. Annotation, filtering and classification of variant detection, according to ACMG evidence were implement- ed using several databases and tools (ClinVar, HGMD, ddSNP, AD genome, UniPort, Franklin Genoox). Detailed analyzes of different genes as classified variants as well as pathogenic changes based on the ClinVar database and changes in nonsense, frameshift, inframe, splice sequences as well as star/stop codon with mutation, which with frequency global is less than 5%. Conclusions- PCR amplification of exon 21 from the MED12 gene and direct sequencing with BigDye, sequence terminator and gel are according to the Sanger method and analysis on the automatic analyzer ABI-PRISM 3500. The results show that the MED12 gene is located on the X chromosome and encodes the so-called protein intermediate complex with subunit 12 and is part of the group of about 25 types of proteins that form the protein complex with genetic regulatory function. The MED12 pro- tein is involved in many aspects during early development, such as in nerve cells (neurons) in the brain (Medlineplus: MED12). Pathogenic variants in the MED12 gene are responsible for MED12 associated with disordered development of the nervous sys- tem, of which the group causes disease and is linked to the sex chromosome X. Linked defects for the MED12 gene present phe- notypes in the FG-type syndrome (FGS1), X-linked Lujan syndrome (LS).

Keywords:

MED12 gene, CeGaT GmbH Tubingen, ClinVar, PCR

Proceedings Editor

Edmond Hajrizi

ISBN

978-9951-982-15-3

Location

UBT Kampus, Lipjan

Start Date

25-10-2024 9:00 AM

End Date

27-10-2024 6:00 PM

DOI

10.33107/ubt-ic.2024.355

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Oct 25th, 9:00 AM Oct 27th, 6:00 PM

Genetic and Psychiatric Molecular Analysis in Speech Delay Syndrome

UBT Kampus, Lipjan

The work in is a special genetic case and the goal is to know the type of mutation, the genesis of this hitherto unknown case. This study included a population of 9000 individuals in the northern part of Macedonia. During the family interviews, we came across the case of a boy who had speech impediments, aggressive behavior and small deformities in the size of his nose, ears and face. The 5year-old male had slurred voices, not formulating meaningful words that were unclear. Summary- First EEG and genetic analyzes were done. The case at the age of 2 correctly emphasized words such as nana, grandfather, grandmother, but then lost the words. From the questionnaire, they stated that the grandmother's loud voice created stress in the child and they have been living in another region for 3 years, but the changes are very small in speech. Methods and analyses-From targeted genetic analysis such as massively parallel sequencing (Next Generation Sequencing, NGS) in exons of up to 99% of protein-coding genes (Whole Exome Sequencing, WES) for new sequencing with 6000 sequenc- ers. Bioinformatic analyzes for sequencer mapping of fragments as a reference for variants are processed based on Hg19 versions in the human genome reference. Sequencing and analysis were performed at the accredited reference laboratory - CeGaT GmbH, Tubingen, Germany. Annotation, filtering and classification of variant detection, according to ACMG evidence were implement- ed using several databases and tools (ClinVar, HGMD, ddSNP, AD genome, UniPort, Franklin Genoox). Detailed analyzes of different genes as classified variants as well as pathogenic changes based on the ClinVar database and changes in nonsense, frameshift, inframe, splice sequences as well as star/stop codon with mutation, which with frequency global is less than 5%. Conclusions- PCR amplification of exon 21 from the MED12 gene and direct sequencing with BigDye, sequence terminator and gel are according to the Sanger method and analysis on the automatic analyzer ABI-PRISM 3500. The results show that the MED12 gene is located on the X chromosome and encodes the so-called protein intermediate complex with subunit 12 and is part of the group of about 25 types of proteins that form the protein complex with genetic regulatory function. The MED12 pro- tein is involved in many aspects during early development, such as in nerve cells (neurons) in the brain (Medlineplus: MED12). Pathogenic variants in the MED12 gene are responsible for MED12 associated with disordered development of the nervous sys- tem, of which the group causes disease and is linked to the sex chromosome X. Linked defects for the MED12 gene present phe- notypes in the FG-type syndrome (FGS1), X-linked Lujan syndrome (LS).