Objectives: Identify the best indicator to detect genetic pathologic variants (PV) in clinical exome studies, in a referral population with developmental problems. Patients and interventions: Two years(21-22) ambispective cohort study on 100 patients referred to our health area (Reference for 23,909 children < 15 y-o), for different developmental disorders who are indicated for a clinical exome study because of the following indicator factors (IF): Mental retardation (MR), ASD, motor delay (MD), epilepsy (EP) and physical malformations (PHM). The presence of PV is assessed and the number of variants of uncertain significance (VUS) is compared between those who present an IF and those who do not. The relative risk (RR) of presenting or not presenting PV is analysed, as well as the differences in the mean total number of VUS between those who present or not one of the indication factors (student-t). Results: In 61 cases of the 100, PV were found. Patients with MR presented an RR = 1.56 (1.1-2.3) compared to patients who did not have it. In patients with MR the mean number was VUS=33+-13.6, significantly higher (p=0.04) than those without Non_MR VUS=27+-12.7. ASD, MD, and PHM did not show significant risk values either in frequency of VP or VUS. Conclusions: 1) MR is the main individual indicator of risk of PV in the exome in our healthcare reference area. 2) The other recommended exome study indicators, individually, did not represent a significant increase in the risk of PV or VUSI over those who did not present them.

ISABEL MARIA LUCAS-REQUENA
General University Hospital of Elche
Spain

MAITE LÓPEZ-GARRIGOS
UNIVERSITY HOSPITAL OF SAN JUAN DE ALICANTE
Spain

Samantha Turner
UNIVERSITY HOSPITAL OF SAN JUAN DE ALICANTE
Spain

Lorena Pastor-Ferrandiz
UNIVERSITY HOSPITAL OF SAN JUAN DE ALICANTE
Spain

Patricia Andreo-Lillo
UNIVERSITY HOSPITAL OF SAN JUAN DE ALICANTE
Spain

Francisco Carratalá-Marco
UNIVERSITY HOSPITAL OF SAN JUAN DE ALICANTE. Miguel Hernandez University
Spain