The3M syndrome is inherited via an autosomal recessive pattern and most likely appear withmutations on the 3 genes .
(21). The molecular studies of 3M syndrome shows that Most of the Mutationtypes appearing on the 8 exons that encoding Ig domains of OBSL1 proteins (22). (23). In our case, on theother hand, we detected that a novel nonsense mutation on OBSL1 gene isthe cause of 3M syndrome. New studies about of OBSL1 gene and protein suggestedthat the OBSL1 protein functions in cytoskeletaladaptor.
This protein linking the nuclear proteins to the cytoplasmic supportnetwork. Additionally, other studies showed function as a scaffold protein.(24) obvioussupposed disruptionof OBSL1 protein by mutation causes skeletal or cardiac myopathy , because the scaffoldsignaling complexes and cytoskeletalnetwork Depended on OBSL1proteinfunction.(27).Additionaly, IGFBP-2 and IGFB5 messenger ribonucleicacid levels collaborated with OBSL1 mutations in 3M syndrome (25 26). In our current investigation,c.842G>A mutation likely induce the growth-regulatory pathway. it isunfortunate that, specific treatment for 3M syndrome not exist (28).
However,some researcherssuggestedusing of human growth hormone (GH) for treatment. This mutation was identifiedusing the targeted NGS method and were confirmed by Sanger sequencing, on OBSL1gene, where reported as MSBN-causingmutation, that were not previously reported in the Iranian population. Theclinical assessment for short stature is most important symptom to 3M diagnosis.However, the 3M syndrome can identify via differential diagnosis like with mildsymptomatology and wide variety of causal factors.Therefore, the molecular diagnosis hasuseful and important implications for the family.
Once a mutation was found inthe proband, carrier determination should be performed for other relatedasymptomatic family members. Unfortunately, family members of the proband werenot available for segregation analysis.the 3M syndrome have autosomal recessivepattern, Due to the fact for these Disorders,early diagnosis with moleculartesting and genetic counselling Helpfulfor other member of family. Patient with symptom of 3M syndrome like growth failure have characteristic symptoms to dogenetic testing.
.Itis therefore concluded that NGS is an excellent method to determine all typesof disease causing and novel mutations on 3M gene. With NGS we are able todetermine deletions, duplications and small mutations which can cause 3Msyndrome in single experiment assay. The development of genetics and theavailability of high throughput screening technology provide a greatopportunity to identify gene variants that may explain disease phenotypes.
Thisreport is the first study to screen for mutations in 3-M syndrome genes inclinically diagnosed patients from Iran. It confirms the genetic heterogeneityof 3-M syndrome in Iran, and shows the importance of using NGS genetic testingto confirm the diagnosis.