{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T12:28:20Z","timestamp":1761740900750,"version":"build-2065373602"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      3M syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the cullin 7 (\n                      <jats:italic>CUL7<\/jats:italic>\n                      ), obscurin-like 1 (\n                      <jats:italic>OBSL1<\/jats:italic>\n                      ), and coiled-coil domain-containing protein 8 (\n                      <jats:italic>CCDC8<\/jats:italic>\n                      ) genes and is characterized by pre- and postnatal growth retardation, short stature, dysmorphic facial features, and skeletal anomalies, with normal intelligence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      In this study, we report a 6-year-old female patient from China diagnosed with 3M syndrome. The patient presented with typical clinical features of growth retardation and short stature, with normal intelligence. The patient\u2019s dysmorphic facial features included relative macrocephaly, a protruding forehead, a triangular face, a pointed chin, a flat nasal bridge, full lips, a long philtrum, and a broad lower jaw. The skeletal survey was normal except for clinodactyly of the fifth fingers of both hands. Growth hormone (GH) deficiency was excluded by normal serum hormone levels and the GH stimulation test results. Whole-exome sequencing identified two heterozygous variants in\n                      <jats:italic>CUL7<\/jats:italic>\n                      , NM_014780.5: c.1639_1640del (p.Leu547Alafs*6), and NM_014780.5: c.4505T&amp;gt;C (p.Ile1502Thr). Parental Sanger sequencing confirmed these as compound heterozygous variants, with one variant inherited from each parent. Neither variant has been previously reported. The patient has been treated with recombinant human IGF-1 for 2\u2005years since she was 4\u2005years old and has achieved a growth velocity of approximately 6\u20137\u2005cm per year.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Herein, we describe a Chinese patient with 3M syndrome caused by novel biallelic pathogenic variants in\n                      <jats:italic>CUL7<\/jats:italic>\n                      from a non-consanguineous family, expanding the genetic spectrum of\n                      <jats:italic>CUL7<\/jats:italic>\n                      in the Chinese population.\n                    <\/jats:p>\n                  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