{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T05:35:56Z","timestamp":1767591356856,"version":"3.48.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Growth Hormone (GH), secreted by the anterior pituitary gland, is a key regulator of postnatal growth. Mutations in the\n                      <jats:italic>GH1<\/jats:italic>\n                      gene can lead to isolated GH deficiency (IGHD), a rare disorder characterized by growth failure and severe short stature. The aim of this study was to identify the genetic basis of IGHD in three siblings born to consanguineous parents.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Three siblings were diagnosed with short stature due to GH deficiency (stimulated GH peak levels between 0.07 and 0.77 \u00b5g\/L). To identify their genetic cause, whole-exome sequencing (WES), multiplex ligation-dependent probe amplification (MLPA), and targeted\n                      <jats:italic>GH1<\/jats:italic>\n                      sequencing was performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A shared homozygous\n                      <jats:italic>GH1<\/jats:italic>\n                      haplotype comprising nine single nucleotide polymorphisms (SNPs), spanning the promoter, coding, and 3\u2019 flanking regions, was revealed. The parents were heterozygous carriers of this haplotype. This rare SNP combination (with less than 1% population frequency) overlaps with transcriptional regulatory elements and has previously been associated with significantly reduced promoter activity (58% promoter activation relative to wild-type). No pathogenic coding mutations or deletions were identified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings suggest that this haplotype likely underlies the GH deficiency observed in the affected siblings. This represents the first report linking a homozygous\n                      <jats:italic>GH1<\/jats:italic>\n                      promoter haplotype to IGHD, underscoring the role of noncoding variants in endocrine disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1704842","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T05:31:48Z","timestamp":1767591108000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Growth hormone deficiency in three siblings homozygous for a rare GH1 haplotype"],"prefix":"10.3389","volume":"16","author":[{"given":"Ana Cl\u00e1udia","family":"Ribeiro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omneya 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