{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:13:30Z","timestamp":1791296010492,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2010,9,3]],"date-time":"2010-09-03T00:00:00Z","timestamp":1283472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The <jats:italic>COL4A1<\/jats:italic> gene encodes the \u03b11\u2010chain of type IV collagen, which is ubiquitously expressed in basement membranes. Mutations in <jats:italic>COL4A1<\/jats:italic> have been reported in autosomal\u2010dominant porencephaly and in patients with symptomatic small vessel brain disease, inconstantly associated with eye defects. We have previously reported three <jats:italic>COL4A1<\/jats:italic> mutations associated with a systemic phenotype that we called HANAC (Hereditary Angiopathy, Nephropathy, Aneurysms, and Cramps). We carried out a clinical and genetic study of three families presenting with characteristic features of HANAC syndrome. Common systemic signs included arterial retinal tortuosity and muscle cramps, with a variable combination of small vessel brain disease, Raynaud phenomena, and kidney defects. Three novel <jats:italic>COL4A1<\/jats:italic> missense substitutions are described, which affect highly conserved glycine residues within the collagenous domain of the protein. All six known mutations associated with the HANAC phenotype are localized within the CB3[IV] fragment of COL4A1, which encompasses major integrin\u2010binding sites. Our results confirm that HANAC syndrome is a distinct clinical entity within the <jats:italic>COL4A1<\/jats:italic>\u2010related disorders, which is characterized by systemic involvement and usually asymptomatic brain disease. The restricted distribution of <jats:italic>COL4A1<\/jats:italic> mutations within the CB3[IV] region is a characteristic of the reports of patients with HANAC, which suggests that abnormal cell\u2010type IV collagen interactions may underlie the systemic defects observed in this syndrome. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33659","type":"journal-article","created":{"date-parts":[[2010,9,5]],"date-time":"2010-09-05T06:44:47Z","timestamp":1283669087000},"page":"2550-2555","source":"Crossref","is-referenced-by-count":93,"title":["Novel <i>COL4A1<\/i> mutations associated with HANAC syndrome: A role for the triple helical CB3[IV] domain"],"prefix":"10.1002","volume":"152A","author":[{"given":"Emmanuelle","family":"Plaisier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gekeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa","family":"Benhassine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Dahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Marro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Alamowitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Paques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Ronco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,9,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181c3fd12"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.04.014"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.035584"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21525"},{"key":"e_1_2_6_6_1","first-page":"4765","article-title":"The a1b1 integrin recognition site of basement membrane collagen molecule [a1(IV)2 a2(IV)]","volume":"12","author":"Eble JA","year":"1993","journal-title":"EMBO J"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.124.10.1492"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109418"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa053727"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm024"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.7.1218"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.20564"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00341.x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071906"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.10569"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2009.04.010"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21191"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.106.475194"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi348"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp584"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20715"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.33659","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33659","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T05:54:12Z","timestamp":1697003652000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,3]]},"references-count":20,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2010,10]]}},"alternative-id":["10.1002\/ajmg.a.33659"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33659","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,3]]}}}