{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T22:44:28Z","timestamp":1757544268180,"version":"3.40.5"},"reference-count":10,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T00:00:00Z","timestamp":1576108800000},"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":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pontocerebellar hypoplasia type 9 (PCH9) is an autosomal recessive neurodevelopmental disorder caused by pathogenic variants in the <jats:italic>AMPD2<\/jats:italic> gene. We evaluated the son of a consanguineous couple who presented with profound hypotonia and global developmental delay. Other features included sensorineural hearing loss, asymmetric astigmatism, and high myopia. Clinical whole\u2010exome sequence analysis identified a homozygous missense variant in <jats:italic>AMPD2<\/jats:italic> (NM_001257360.1:c.2201C\u2009&gt; T, p.[Pro734Leu]) that has not been previously reported. Given the strong phenotypic overlap with PCH9, including the identification of the typical \u201cFigure 8\u201d appearance of the brainstem on neuroimaging, we suspect this variant was causative of the neurodevelopmental disability in this individual. An additional homozygous nonsense variant in <jats:italic>COL11A1<\/jats:italic> (NM_001854.4:c.1168G\u2009&gt;\u2009T, p.[Glu390Ter]) was identified. Variants in this alternatively spliced region of <jats:italic>COL11A1<\/jats:italic> have been identified to cause an autosomal recessive form of Stickler syndrome type 2 characterized by sensorineural hearing loss and eye abnormalities, but without musculoskeletal abnormalities. The <jats:italic>COL11A1<\/jats:italic> variant likely also contributed to the individual's phenotype, suggesting two potentially relevant genetic findings. This challenging case highlights the importance of detailed phenotypic characterization when interpreting whole exome data.<\/jats:p>","DOI":"10.1002\/ajmg.a.61452","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T06:34:57Z","timestamp":1576218897000},"page":"557-560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Homozygous variants in <i>AMPD2<\/i> and <i>COL11A1<\/i> lead to a complex phenotype of pontocerebellar hypoplasia type 9 and Stickler syndrome type 2"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8288-6268","authenticated-orcid":false,"given":"Nicolas J.","family":"Abreu","sequence":"first","affiliation":[{"name":"The Center for Gene Therapy  Columbus Ohio"},{"name":"Department of Pediatrics The Ohio State University  Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C.","family":"Koboldt","sequence":"additional","affiliation":[{"name":"The Institute for Genomic Medicine at Nationwide Children's Hospital  Columbus Ohio"},{"name":"Department of Pediatrics The Ohio State University  Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie M.","family":"Gastier\u2010Foster","sequence":"additional","affiliation":[{"name":"The Institute for Genomic Medicine at Nationwide Children's Hospital  Columbus Ohio"},{"name":"Department of Pediatrics The Ohio State University  Columbus Ohio"},{"name":"Department of Pathology The Ohio State University  Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashita","family":"Dave\u2010Wala","sequence":"additional","affiliation":[{"name":"The Institute for Genomic Medicine at Nationwide Children's Hospital  Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin M.","family":"Flanigan","sequence":"additional","affiliation":[{"name":"The Center for Gene Therapy  Columbus Ohio"},{"name":"Department of Pediatrics The Ohio State University  Columbus Ohio"},{"name":"Department of Neurology The Ohio State University  Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9621-8319","authenticated-orcid":false,"given":"Megan A.","family":"Waldrop","sequence":"additional","affiliation":[{"name":"The Center for Gene Therapy  Columbus Ohio"},{"name":"Department of Pediatrics The Ohio State University  Columbus Ohio"},{"name":"Department of Neurology The Ohio State University  Columbus 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