{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:26:30Z","timestamp":1791476790817,"version":"4.3.4"},"reference-count":5,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18ek0109301s2201"],"award-info":[{"award-number":["18ek0109301s2201"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noonan syndrome\u2010like disorder with loose anagen hair (NSLH) is a rare disease characterized by typical features of Noonan syndrome with additional findings of relative or absolute macrocephaly, loose anagen hair, and a higher incidence of intellectual disability. NSLH1 is caused by a heterozygous mutation in the <jats:italic>SHOC2<\/jats:italic> gene on chromosome 10q25, and NLSH2 is caused by a heterozygous mutation in the <jats:italic>Protein phosphatase one catalytic subunit beta<\/jats:italic> (<jats:italic>PPP1CB<\/jats:italic>) gene on chromosome 2p23. Protein phosphatase1 (PP1), encoded by <jats:italic>PPP1CB,<\/jats:italic> forms a complex with SHOC2 and dephosphorylates RAFs, which results in activation of the signaling cascade and contribution to Noonan syndrome pathogenesis. Here, we report two genetically confirmed Japanese patients with NSLH2 having the same de novo mutation in <jats:italic>PPP1CB<\/jats:italic> presenting prominent\u2014hyperteloric\u2014appearing eyes and a tall forehead similar to individuals carrying a mutation in PPP1CB, c.146C\u2009&gt;\u2009G; p.Pro49Arg, which is different from typical facial features of Noonan syndrome. They also showed short stature, absolute macrocephaly, and loose anagen hair like NSLH1: however, growth hormone deficiency often seen in NSLH1 caused by <jats:italic>SHOC2<\/jats:italic> mutation was absent. Although a number of Noonan syndrome and NSLH1 patients have shown blunted or no response to GH therapy, linear growth was promoted by recombinant human growth hormone (rhGH) in one of our patients. Since another NSLH2 patient with good response to rhGH treatment was reported, rhGH therapy may be effective in patients with NSLH2.<\/jats:p>","DOI":"10.1002\/ajmg.a.62733","type":"journal-article","created":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T06:59:39Z","timestamp":1648277979000},"page":"2246-2250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Two Japanese patients with Noonan syndrome\u2010like disorder with loose anagen hair 2"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-5757","authenticated-orcid":false,"given":"Kaori","family":"Maruwaka","sequence":"first","affiliation":[{"name":"Department of Pediatrics Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine  Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaharu","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taihei","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-6129","authenticated-orcid":false,"given":"Rika","family":"Kosaki","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehito","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics, Institute for Comprehensive Medical Science Fujita Health University  Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenjiro","family":"Kosaki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5690-5218","authenticated-orcid":false,"given":"Hiroki","family":"Kurahashi","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics, Institute for Comprehensive Medical Science Fujita Health University  Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38070"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37781"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-016-1731-1"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38056"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61638"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62733","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62733","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62733","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T08:55:50Z","timestamp":1692867350000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,25]]},"references-count":5,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/ajmg.a.62733"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62733","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,25]]},"assertion":[{"value":"2021-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}