{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:59:53Z","timestamp":1791295193586,"version":"4.1.0"},"reference-count":51,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2012,11,13]]},"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder, affecting an estimated 1\u2009:\u20092000\u20134000 live births. Patients with 22q11.2DS have a broad spectrum of phenotypic abnormalities which generally includes congenital cardiac abnormalities, palatal anomalies, and immunodeficiency. Additional findings, such as skeletal anomalies and autoimmune disorders, can confer significant morbidity in a subset of patients. 22q11.2DS is a contiguous gene DS and over 40 genes are deleted in patients; thus deletion of several genes within this region contributes to the clinical features. Mutations outside or on the remaining 22q11.2 allele are also known to modify the phenotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We utilised whole exome, targeted exome and\/or Sanger sequencing to examine the genome of 17 patients with 22q11.2 deletions and phenotypic features found in &lt;10% of affected individuals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results and conclusions<\/jats:title>\n                  <jats:p>In four unrelated patients, we identified three novel mutations in <jats:italic>SNAP29<\/jats:italic>, the gene implicated in the autosomal recessive condition cerebral dysgenesis, neuropathy, ichthyosis and keratoderma (CEDNIK). <jats:italic>SNAP29<\/jats:italic> maps to 22q11.2 and encodes a soluble SNARE protein that is predicted to mediate vesicle fusion at the endoplasmic reticulum or Golgi membranes. This work confirms that the phenotypic variability observed in a subset of patients with 22q11.2DS is due to mutations on the non-deleted chromosome, which leads to unmasking of autosomal recessive conditions such as CEDNIK, Kousseff, and a potentially autosomal recessive form of Opitz G\/BBB syndrome. Furthermore, our work implicates <jats:italic>SNAP29<\/jats:italic> as a major modifier of variable expressivity in 22q11.2 DS patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2012-101320","type":"journal-article","created":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T23:33:56Z","timestamp":1355268836000},"page":"80-90","source":"Crossref","is-referenced-by-count":103,"title":["Hemizygous mutations in SNAP29 unmask autosomal recessive conditions and contribute to atypical findings in patients with 22q11.2DS"],"prefix":"10.1136","volume":"50","author":[{"given":"Donna M","family":"McDonald-McGinn","sequence":"first","affiliation":[{"name":"Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somayyeh","family":"Fahiminiya","sequence":"additional","affiliation":[{"name":"Department of 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T","family":"Bilaniuk","sequence":"additional","affiliation":[{"name":"Division of Neuroradiology, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen E","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Division of Allergy Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly S","family":"Emanuel","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania 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