Clinical and molecular profile of an Iranian patient with homozygous mutation in LARP۷ gene leading to Alazami syndrome

Background and Aim: Alazami syndrome is a rare genetic disorder described by hallmark features such as primordial dwarfism, severe intellectual disability, and distinct facial feature. Homozygous or compound heterozygous mutations in LARP۷ gene lead to Alazami syndrome. This gene codes for chaperone protein of noncoding RNA ۷SK. To date, ۲۳ patients from ۱۱ families have been recognized with Alazami syndrome in the literature. Here, we describe clinical and molecular characteristics of an Iranian patient with Alazami syndrome.Methods: In this study a ۱۵-month-old patient with clinical features related to growth retardation has been evaluated. She was referred to the Akbar hospital pediatric endocrinology department, Mashhad, Iran to be investigated. clinical assessments were performed in clinic. To conduct a genetic evaluation, Genomic DNA was extracted from PBMC and whole exome sequencing was accomplished.Results: Patient has been diagnosed with clinical manifestations of Alazami syndrome compared with those reported in previous studies including short stature, severe intellectual disability, some distinct dysmorphic facial features such as triangular face, deep set eyes, low set ears, and short philtrum. She also exhibited behavioral problem related to anxiety. Whole exome sequencing revealed a novel homozygous pathogenic frameshift deletion (c.۱۰۹۰_۱۰۹۳del; p. K۳۶۴Rfs*۱۱), in exon ۸ LARP۷ gene. Protein modeling illustrates that this mutation has deleterious effect on protein structure of LARP۷ gene confirming the clinical diagnosis of Alazami syndrome. Segregation analysis in the parents of the proband further confirmed the causative nature of this mutation.Conclusion: This study presents a novel deleterious mutation related to Alazami syndrome, which confirms the phenotypic manifestations of this condition. Moreover, it provides differential diagnosis for growth retardation and intellectual disability. This family can now use PND to prevent the disease in their next pregnancy.

کلیدواژه ها:

Alazami syndrome ، LARP۷ ، intellectual disability ، primordial dwarfism