Vol.:(0123456789) 1 3 Molecular Biology Reports https://doi.org/10.1007/s11033-020-05743-6 ORIGINAL ARTICLE Implementation of chromosomal microarrays in a cohort of patients with intellectual disability at the Argentinean public health system Lucía Daniela Espeche 1  · Andrea Paula Solari 1  · María Ángeles Mori 2,3,4  · Rubén Martín Arenas 2,3,4  · María Palomares 2,3,4  · Myriam Pérez 1  · Cinthia Martínez 1  · Vanesa Lotersztein 1  · Mabel Segovia 1  · Romina Armando 5  · Liliana Beatriz Dain 1  · Julián Nevado 2,3,4  · Pablo Lapunzina 2,3,4  · Sandra Rozental 1 Received: 3 February 2020 / Accepted: 28 August 2020 © Springer Nature B.V. 2020 Abstract Intellectual disability is a neurodevelopmental disorder in which genetic, epigenetic and environmental factors are involved. In consequence, the determination of its etiology is usually complex. Though many countries have migrated from conven- tional cytogenetic analysis to chromosomal microarrays as the frst-tier genetic test for patients with this condition, this last technique was implemented in our country a few years ago. We report on the results of the implementation of chromosomal microarrays in a cohort of 133 patients with intellectual disability and dysmorphic features, normal karyotype and normal subtelomeric MLPA results in an Argentinean public health institution. Clinically relevant copy number variants were found in 12% of the patients and one or more copy number variants classifed as variants of uncertain signifcance were found in 5.3% of them. Although the diagnostic yield of chromosomal microarrays is greater than conventional cytogenetics for these patients, there are fnancial limitations to adopt this technique as a frst-tier test in our country, especially in the public health system. Keywords CMA · Chromosomal microarray · arrayCGH · Intellectual disability · CNV Introduction Intellectual disability (ID) is a neurodevelopmental disor- der characterized by signifcant impairment in cognitive functions and in one or more adaptive behaviors with onset before 18 years of age. There are genetic, epigenetic and environmental factors that can afect the development and functioning of the nervous system. In consequence, the determination of the ID etiology is usually complex and requires a multidisciplinary approach. The prevalence of ID varies depending on the criteria used in the diagnosis as well as on the population’s socio- economic level. In developed countries, the prevalence is thought to be between 2 and 3% but it is higher in countries of lower socioeconomic status [1]. Severe ID is relatively stable and seems to be caused mostly by genetic factors in about 25% to 50% of ID patients [2]. This stresses the impor- tance of genetic assessment for the diagnosis and prevention of the recurrence of ID, being this condition, therefore, a common reason for referral to a genetic clinic. ID may occur either in isolation (non-syndromic) or in conjunction with other clinical manifestations as part of a recognizable syndrome (e.g. Down syndrome). Neverthe- less, only in a handful of patients their clinical features indi- cate a defned chromosomic or monogenic condition and guide the choice of specifc genetic tests. Cytogenetic analysis (GTG-banding karyotyping) was for a long time the frst step for genetic testing in patients with ID without a clinical presumptive diagnosis. Aneuploi- dies and unbalanced structural rearrangements visible on * Sandra Rozental sandrarozental@yahoo.com.ar 1 Centro Nacional de Genética Médica “Dr. Eduardo Castilla”- ANLIS “Dr. Carlos G. Malbrán”, Ministerio de Salud, Buenos Aires, Argentina 2 Instituto de Genética Médica y Molecular (INGEMM), IdiPAZ, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain 3 CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), ISCIII, Madrid, Spain 4 ITHACA European Reference Network, Madrid, Spain 5 Servicio de Genética, Hospital de Niños “Dr. Ricardo Gutiérrez”, Buenos Aires, Argentina