A Case of Maternal Balanced Transiocation (4p; 8p) and three affected Progeny: Genotype Phenotype Correlation Study

Abstract

Background: Idiopathic mental retardation also known as intellectual disability is the condition associated with genetic abnormalities and environmental factors. Genetic causes of mental retardation are numerical and structural chromosomal abnormalities. Translocation is one of the most studied chromosomal abnormalities in which a portion of one chromosome breaks and reattaches to the non homologous chromosome. This leads to spontaneous abortion of fetus and a child with various anomalies. The present case is of a familial case, in which maternal chromosome have balanced translocation (4p;8p) and three live progeny with unbalanced chromosome translocation (4p;8p) between five spontaneous abortions. All three progeny are having mental retardation and abnormal phenotype. Aim: The present study is carried out to know the genes involved in maternal balanced translocation and the genes which may sponsible for abnormal phenotype and mental retardation in progeny. Method: To confirm the translocation in maternal genome microarray was performed. The findings of molecular studies of progeny were further assessed using bioinformatics tools. Phenotype-Genotype correlation was performed using OMIM and ClinGen Genome Dosage Map. Result: In this study we confirm that the maternal genome has balanced kind of translocation and which affect three progeny by mitotic adjacent-1 segregation and lead to partial monosomy 8p and partial trisomy 4p. The biological function assessment of clinically relevant genes in three progeny via PANTHER showed high association with metabolic or cellular processes. We also found presence of OMIM genes on chromosome 4p and 8p which might be responsible for abnormal phenotype and mental retardation in progeny. Presence of clinically important dosage sensitive genes which might be responsible for abnormal phenotype were found via ClinGen Genome Dosage Map.