{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:25:35Z","timestamp":1789410335178,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T00:00:00Z","timestamp":1444089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["1ZIAHD008898\u201002"],"award-info":[{"award-number":["1ZIAHD008898\u201002"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000056","name":"National Institute of Nursing Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000056","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Sleep Research"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    In rodent studies, paired box 6 (\n                    <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>\n                    6) appears to play an important role in the development of the pineal, the primary source of the circadian regulating hormone, melatonin. Pineal hypoplasia has been previously reported in patients with\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>\n                      6\n                    <\/jats:italic>\n                    haploinsufficiency (+\/\u2212); however, pineal measurement, melatonin concentrations and sleep quality have not been reported. This cross\u2010sectional descriptive study examined pineal volume, melatonin secretion and sleep disturbance in 37 patients with\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>\n                      6\n                    <\/jats:italic>\n                    +\/\u2212 (age 15.3\u00a0\u00b1\u00a09.9\u00a0years) and 17 healthy controls (16.0\u00a0\u00b1\u00a07.2\u00a0years), within an inpatient setting at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland,\n                    <jats:styled-content style=\"fixed-case\">USA<\/jats:styled-content>\n                    . Pineal volume was evaluated by magnetic resonance imaging. Diurnal serum cortisol, serum melatonin and urine 6\u2010sulphatoxymelatonin concentrations were measured by enzyme\u2010linked immunosorbent assay. The Child Sleep Habits Questionnaire was administered for patients &lt;13\u00a0years old. Pineal volume was fivefold lower in\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>\n                      6\n                    <\/jats:italic>\n                    +\/\u2212 versus controls (mean\u00a0\u00b1\u00a0\n                    <jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>\n                    : 25\u00a0\u00b1\u00a015 versus 129\u00a0\u00b1\u00a050\u00a0\n                    <jats:italic>\u03bc<\/jats:italic>\n                    L,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.001). Midnight serum cortisol was similar in\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>\n                      6\n                    <\/jats:italic>\n                    +\/\u2212 versus controls (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.14). Midnight serum melatonin was &gt;\u00a0twofold lower in\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>\n                      6\n                    <\/jats:italic>\n                    +\/\u2212 versus controls [median (25th\u201375th): 28 (22\u201342) versus 71 (46\u201388)\u00a0pg\u00a0\n                    <jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>\n                    <jats:sup>\u22121<\/jats:sup>\n                    ,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.001]. First morning void urinary 6\u2010sulphatoxymelatonin was fourfold lower in\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>\n                      6\n                    <\/jats:italic>\n                    +\/\u2212 versus controls [11 (6\u201326) versus 45 (34\u201361)\u00a0ng\u00a0mg\n                    <jats:sup>\u22121<\/jats:sup>\n                    Cr,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.001]. Child Sleep Habits Questionnaire score was higher in\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>\n                      6\n                    <\/jats:italic>\n                    +\/\u2212 versus controls (48\u00a0\u00b1\u00a06 versus 41\u00a0\u00b1\u00a05,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.03). The current findings suggest that\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>\n                      6\n                    <\/jats:italic>\n                    +\/\u2212 is associated with smaller pineal size, lower melatonin secretion and greater parental report of sleep disturbances in children. Further studies are needed to explore the potential use of melatonin replacement for improving sleep quality in patients with\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>\n                      6\n                    <\/jats:italic>\n                    +\/\u2212.\n                  <\/jats:p>","DOI":"10.1111\/jsr.12345","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T02:49:01Z","timestamp":1444099741000},"page":"16-22","source":"Crossref","is-referenced-by-count":28,"title":["Pineal hypoplasia, reduced melatonin and sleep disturbance in patients with\n                    <i>\n                      <scp>PAX<\/scp>\n                      6\n                    <\/i>\n                    haploinsufficiency"],"prefix":"10.1111","volume":"25","author":[{"given":"Alyson E.","family":"Hanish","sequence":"first","affiliation":[{"name":"Section\u00a0on Growth and Obesity Program in Developmental Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health (NIH) Bethesda MD USA"},{"name":"National Institute of Nursing Research NIH Bethesda MD USA"},{"name":"College of Nursing University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Butman","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences Clinical Center NIH Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francine","family":"Thomas","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences Clinical Center NIH Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Yao","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences Clinical Center NIH Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan C.","family":"Han","sequence":"additional","affiliation":[{"name":"Section\u00a0on Growth and Obesity Program in Developmental Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,6]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"2074","article-title":"PAX6 aniridia and interhemispheric brain anomalies","volume":"15","author":"Abouzeid H.","year":"2009","journal-title":"Mol. 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