{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T02:26:03Z","timestamp":1766975163815,"version":"3.48.0"},"reference-count":9,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Childhood\u2010onset neurodegeneration with progressive microcephaly (CONPM) is a rare autosomal recessive disorder caused by pathogenic variants in the\n                    <jats:italic>DTYMK<\/jats:italic>\n                    gene. This ultra\u2010rare condition is characterized by progressive neurological regression, epilepsy, severe microcephaly, and global cerebral atrophy. Only four cases have been reported in the literature to date. This paper's objective is to describe the fifth globally reported case of CONPM and the first documented in a Mexican patient, confirmed through whole\u2010exome sequencing (WES), and to compare findings with previously reported cases. Clinical evaluation, neuroimaging studies, and genetic analysis using WES followed by Sanger sequencing were performed. Clinical and genetic data were analyzed in the context of existing literature on CONPM. A 2\u2010year\u2010old male with progressive neurodevelopmental regression presented with severe microcephaly, epilepsy, hypertonia, and cortical and cerebellar atrophy. Genetic analysis identified a homozygous missense variant in\n                    <jats:italic>DTYMK<\/jats:italic>\n                    (NM_012145.4:c.242C&gt;T; p.Pro81Leu). This variant is predicted to disrupt dTMP phosphorylation, a key step in the maintenance of dTTP pools required for genomic stability and neural function. This case expands the known phenotypic and genotypic spectrum of CONPM and underscores the importance of considering DTYMK variants in cases of childhood neurodegeneration with microcephaly. Further functional studies are needed to elucidate the mechanisms linking DTYMK dysfunction to neurodegeneration.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64187","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T06:24:57Z","timestamp":1753251897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Childhood\u2010Onset Neurodegeneration With Progressive Microcephaly (\n                    <scp>CONPM<\/scp>\n                    ) due to a\n                    <scp>\n                      <i>DTYMK<\/i>\n                    <\/scp>\n                    Homozygous Pathogenic Variant: Outlining the Phenotype of an Ultra\u2010Rare Disease"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7625-7353","authenticated-orcid":false,"given":"Hern\u00e1ndez\u2010Carreto","family":"Ra\u00fal","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Acosta\u2010Rodr\u00edguez\u2010Bueno Carlos","family":"Patricio","sequence":"additional","affiliation":[{"name":"Clinic of Inborn Errors of Metabolism Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barrag\u00e1n\u2010Arevalo","family":"Tania","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiz\u2010Robles","family":"Osiris","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vald\u00e9s\u2010Ortega Esteban","family":"Alberto","sequence":"additional","affiliation":[{"name":"Department of Imaging Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cer\u00f3n\u2010Rodr\u00edguez","family":"Magdalena","sequence":"additional","affiliation":[{"name":"Clinic of Inborn Errors of Metabolism Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viveros\u2010Rodr\u00edguez Romina","family":"Tamara","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6602-5169","authenticated-orcid":false,"given":"Moreno\u2010Salgado","family":"Rodrigo","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.8.1122"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-013-0177-6"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c05288"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002035"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.06.028"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330\u2010016\u20104454\u20108"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.424"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2017.07.013"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02394-0"}],"container-title":["American Journal of Medical Genetics Part 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