{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T10:21:27Z","timestamp":1776248487507,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":104,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2022J01436"],"award-info":[{"award-number":["2022J01436"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      Hypophosphatasia (HPP) is a rare inborn error of metabolism caused by\n                      <jats:italic>ALPL<\/jats:italic>\n                      gene mutations, resulting in deficient tissue\u2010nonspecific alkaline phosphatase (ALP) activity. We investigated genotype\u2013phenotype correlations in a monozygotic female twin pair with infantile HPP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Peripheral blood samples were collected from two female twins with HPP and their family members. Genomic DNA was extracted, and variations were detected using whole exome sequencing. Zygosity was confirmed via KING 2.3.1 software. Pathogenic variants were validated using Sanger sequencing, mutation analyses, and bioinformatics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The twins presented with bulging anterior fontanel at 3 months of age. At 6 months, serum ALP levels decreased, and skeletal dysplasia, hypercalcemia, and nephrocalcinosis developed. One twin died of pneumonia at 11 months; the other remained alive beyond 15 months. Monochorionic diamniotic placentation and a twin pair kinship coefficient (0.4879) confirmed monozygosity. Exome sequencing revealed that the twins carried compound heterozygous\n                      <jats:italic>ALPL<\/jats:italic>\n                      mutations c.299C&gt;T (p.Thr100Met) and c.1271T&gt;C (p.Val424Ala). The maternally inherited allele c.1271T&gt;C, which was suspected to be pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines, was reported in a homozygous Chinese adult with HPP. The paternally inherited allele c.299C&gt;T was rated as pathogenic by ACMG. In vitro,\n                      <jats:italic>ALPL<\/jats:italic>\n                      c.299C&gt;T\u2010related mutants exhibited reduced residual ALP activity owing to a dominant\u2010negative effect. Analysis of c.299C&gt;T\u2010related mutations in the\n                      <jats:italic>ALPL<\/jats:italic>\n                      Gene Variant Database revealed statistically significant differences in a dominant\u2010negative effect and lower residual ALP activity of allelic mutants in early\u2010onset versus late\u2010onset HPP (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). The dominant\u2010negative effect correlated positively with residual ALP activity (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>s<\/jats:italic>\n                      <\/jats:sub>\n                      = 0.889,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Compound heterozygous\n                      <jats:italic>ALPL<\/jats:italic>\n                      mutations c.299C&gt;T (p.Thr100Met) and c.1271T&gt;C (p.Val424Ala) were causative factors of infantile HPP in the monozygotic twins, providing insights into how dominant\u2010negative effects influence HPP severity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/9913394","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T09:33:57Z","timestamp":1776245637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>ALPL<\/i>\n                    Mutations With Dominant\u2010Negative Effect in Infantile Hypophosphatasia Monozygotic Twins"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3677-3682","authenticated-orcid":false,"given":"Luna","family":"Hao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-9622","authenticated-orcid":false,"given":"Yilun","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juyu","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zekun","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7024-5812","authenticated-orcid":false,"given":"Feng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.20.7666"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(57)90124-9"},{"key":"e_1_2_13_3_2","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/B978-0-12-814841-9.00066-X","volume-title":"Principles of Bone Biology","author":"Whyte M. 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