{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:24:33Z","timestamp":1791476673757,"version":"4.3.4"},"reference-count":25,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T00:00:00Z","timestamp":1443398400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Microcephaly is a fairly common feature observed in children with delayed development, defined as head circumference less than 2 standard deviations below the mean for age and gender. It may be the result of an acquired insult to the brain, such prenatal or perinatal brain injury (congenital infection or hypoxic ischemic encephalopathy), or be a part of a genetic syndrome. There are over 1000 conditions listed in OMIM (Online Mendelian Inheritance in Man) where microcephaly is a key finding; many of these are associated with specific somatic features and non-CNS anomalies. The term primary microcephaly is used when microcephaly and delayed development are the primary features, and they are not part of another recognized syndrome.<\/ns4:p>\n                  <ns4:p>\n                    In this case report, we present the clinical features of siblings (brother and sister) with primary microcephaly and delayed development, and subtle dysmorphic features. Both children had brain MRI studies that showed periventricular and subcortical T2\/FLAIR hyperintensities, without signs of white matter volume loss, and no parenchymal calcifications by CT scan. The family was enrolled in a research study for whole exome sequencing of probands and parents. Analysis of variants determined that the children were compound heterozygotes for nonsense mutations, c.277C&gt;T (p.Arg93*) and c.397C&gt;T (p.Arg133*), in the\n                    <ns4:italic>TRMT10A<\/ns4:italic>\n                    gene. Mutations in this gene have only recently been reported in children with microcephaly and early onset diabetes mellitus.\n                  <\/ns4:p>\n                  <ns4:p>\n                    Our report adds to current knowledge of\n                    <ns4:italic>TRMT10A<\/ns4:italic>\n                    related neurodevelopmental disorders and demonstrates imaging findings suggestive of delayed or abnormal myelination of the white matter in this disorder. Accurate diagnosis through genomic testing, as in the children described here, allows for early detection and management of medical complications, such as diabetes mellitus.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.7106.1","type":"journal-article","created":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T06:40:03Z","timestamp":1443422403000},"page":"912","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities"],"prefix":"10.12688","volume":"4","author":[{"given":"Mohan","family":"Narayanan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keri","family":"Ramsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Grebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-6082","authenticated-orcid":false,"given":"Isabelle","family":"Schrauwen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabolcs","family":"Szelinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Huentelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Craig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinodh","family":"Narayanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"C4RCD 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.7652.r10548, Gihan Tennekoon, Department of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA, 13 Oct 2015, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/4-912\/v1#referee-response-10548","order":0,"name":"referee-response-10548","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.7652.r10547, Ganeshwaran H. Mochida, Pediatric Neurology Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA, 19 Oct 2015, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/4-912\/v1#referee-response-10547","order":1,"name":"referee-response-10547","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by donations to the Center for Rare Childhood Disorders. These include private anonymous donations. TGen also receives support from the State of Arizona. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}