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To the best of our knowledge, no data exists on the genetic architecture of ASD in India. This study aimed to identify the genetic architecture of ASD in India and to assess the use of whole exome sequencing (WES) as a first-tier test instead of chromosomal microarray (CMA) for genetic diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Between 2020 and 2022, 101 patient-parent trios of Indian origin diagnosed with ASD according to the Diagnostic and Statistical Manual, 5th edition, were recruited. All probands underwent a sequential genetic testing pathway consisting of karyotyping, Fragile-X testing (in male probands only), CMA and WES. Candidate variant validation and parental segregation analysis was performed using orthogonal methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 101 trios, no probands were identified with a gross chromosomal anomaly or Fragile-X. Three (2.9%) and 30 (29.7%) trios received a confirmed genetic diagnosis from CMA and WES, respectively. Amongst diagnosis from WES, SNVs were detected in 27 cases (90%) and CNVs in 3 cases (10%), including the 3 CNVs detected from CMA. Segregation analysis showed 66.6% (n\u2009=\u20093 for CNVs and n\u2009=\u200917 for SNVs) and 16.6% (n\u2009=\u20095) of the cases had\n                      <jats:italic>de novo<\/jats:italic>\n                      and recessive variants respectively, which is in concordance with the distribution of variant types and mode of inheritance observed in ASD patients of non-Hispanic white\/ European ethnicity.\n                      <jats:italic>MECP2<\/jats:italic>\n                      gene was the most recurrently mutated gene (n\u2009=\u20096; 20%) in the present cohort. Majority of the affected genes identified in the study cohort are involved in synaptic formation, transcription and its regulation, ubiquitination and chromatin remodeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study suggests\n                      <jats:italic>de novo<\/jats:italic>\n                      variants as a major cause of ASD in the Indian population, with Rett syndrome as the most commonly detected disorder. Furthermore, we provide evidence of a significant difference in the diagnostic yield between CMA (3%) and WES (30%) which supports the implementation of WES as a first-tier test for genetic diagnosis of ASD in India.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12883-023-03341-0","type":"journal-article","created":{"date-parts":[[2023,8,5]],"date-time":"2023-08-05T00:01:23Z","timestamp":1691193683000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Comparative yield of molecular diagnostic algorithms for autism spectrum disorder diagnosis in India: evidence supporting whole exome sequencing as first tier test"],"prefix":"10.1186","volume":"23","author":[{"given":"Frenny","family":"Sheth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhanvi","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepika","family":"Jain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshkumar","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketan","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhaval I","family":"Solanki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand S","family":"Iyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhargavi","family":"Menghani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priti","family":"Mhatre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Bajaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Pandya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Dhami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darshan","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayesh","family":"Sheth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harsh","family":"Sheth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,5]]},"reference":[{"issue":"4","key":"3341_CR1","doi-asserted-by":"crossref","first-page":"560","DOI":"10.3390\/genes12040560","volume":"12","author":"A Arteche-L\u00f3pez","year":"2021","unstructured":"Arteche-L\u00f3pez A, G\u00f3mez Rodr\u00edguez MJ, S\u00e1nchez Calvin MT, Quesada-Espinosa JF, Lezana Rosales JM, Palma Milla C, et al. 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A written informed consent as per the Helsinki Declaration was obtained from the parents and guardians of all probands. All the methods in the study were carried out as per the Helsinki Declaration. The entire dataset presented here does not contain any identifiable information.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"292"}}