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We identified a novel mosaic nonsense variant in the\n                    <jats:italic>PHEX<\/jats:italic>\n                    gene on the X chromosome by next-generation sequencing\u2014c.1971C\u2009&gt;\u2009A, p.(Tyr657X)\u2014\u2013in a man with clinical features of hypophosphatemic rickets. As the variant was only found in 67% of DNA reads, we considered the possibility of sex chromosome aneuploidy (e.g. a 48,XXXY sex chromosome complement with an unaffected X chromosome i.e. variant on 2 of 3 X chromosomes producing a variant allele frequency of approx. 67%) or a postzygotic mutation resulting in the\n                    <jats:italic>PHEX<\/jats:italic>\n                    variant in some but not all cells. His mother was clinically unaffected, and he did not have features of Klinefelter\u2019s syndrome, favouring postzygotic mutation over sex chromosome aneuploidy. We excluded sex chromosome aneuploidy through karyotype studies showing a 46,XY status. As the event must therefore be a postzygotic variant to produce the reduced variant allele frequency, his parents are not at risk of having the variant. However, X chromosome postzygotic mutations in men may be inherited by female offspring (depending on the mosaic status of gonadal tissue). The patient\u2019s karyotype result was thus integral in the investigation of disease mechanism and in guiding family genetic counselling.\n                  <\/jats:p>","DOI":"10.1007\/s00223-025-01388-4","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T14:10:30Z","timestamp":1750255830000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Mosaic PHEX Variant in Hypophosphatemic Rickets: Distinguishing Postzygotic Mutation from Sex Chromosome Aneuploidy"],"prefix":"10.1007","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9197-3999","authenticated-orcid":false,"given":"Wu Tzen","family":"Lim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marni","family":"Nenke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesley","family":"Rawlings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Wells","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra","family":"Vakulin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Waters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunita","family":"De Sousa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"issue":"2","key":"1388_CR1","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1210\/jc.2005-1776","volume":"91","author":"K Goji","year":"2006","unstructured":"Goji K, Ozaki K, Sadewa AH, Nishio H, Matsuo M (2006) Somatic and germline mosaicism for a mutation of the PHEX gene can lead to genetic transmission of X-linked hypophosphatemic rickets that mimics an autosomal doiminant trait. 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