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Yet, both children also presented with early onset obesity. Whole\u2010exome sequencing identified two homozygous substitutions in two genes 170\u00a0kb apart on 7q22.1: a c.1137+1G&gt;T splice mutation in <jats:italic>AP4M1<\/jats:italic> previously described in a familial case of AP4\u2010deficiency syndrome and the <jats:italic>AZGP1<\/jats:italic> c.595A&gt;T missense variant. Haplotyping analysis indicated a founder effect of the <jats:italic>AP4M1<\/jats:italic> mutation, whereas the <jats:italic>AZGP1<\/jats:italic> mutation arose more recently in our family. <jats:italic>AZGP1<\/jats:italic> encodes an adipokine that stimulate lipolysis in adipocytes and regulates body weight in mice. We propose that the siblings' phenotype results from the combined effects of mutations in both <jats:italic>AP4M1<\/jats:italic> and <jats:italic>AZGP1<\/jats:italic> that account for the neurological signs and the morbid obesity of early onset, respectively. Contiguous gene syndromes are the consequence of loss of two or more adjacent genes sensible to gene dosage and the phenotype reflects a combination of endophenotypes. We propose to broaden this concept to phenotypes resulting from independent mutations in two genetically linked genes causing a contiguous mutation syndrome.<\/jats:p>","DOI":"10.1002\/mgg3.134","type":"journal-article","created":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T04:57:17Z","timestamp":1426741037000},"page":"215-220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Contiguous mutation syndrome in the era of high\u2010throughput sequencing"],"prefix":"10.1002","volume":"3","author":[{"given":"Ma\u00e9va","family":"Langou\u00ebt","sequence":"first","affiliation":[{"name":"INSERM UMR 1163 Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders Paris Descartes \u2013 Sorbonne Paris Cit\u00e9 University, Imagine Institute, Necker\u2010Enfants Malades Hospital 75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Siquier\u2010Pernet","sequence":"additional","affiliation":[{"name":"INSERM UMR 1163 Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders Paris Descartes \u2013 Sorbonne Paris Cit\u00e9 University, Imagine Institute, Necker\u2010Enfants Malades Hospital 75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Sanquer","sequence":"additional","affiliation":[{"name":"Metabolic and Proteomic Biochemistry Service Necker\u2010Enfants Malades Hospital AP\u2010HP 75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bole\u2010Feysot","sequence":"additional","affiliation":[{"name":"Genomic Platform INSERM UMR 1163 Paris Descartes \u2013 Sorbonne Paris Cit\u00e9 University, Imagine Institute 75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Nitschke","sequence":"additional","affiliation":[{"name":"Bioinformatic Platform INSERM UMR 1163 Paris Descartes \u2013 Sorbonne Paris Cit\u00e9 University, Imagine Institute 75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Boddaert","sequence":"additional","affiliation":[{"name":"INSERM UMR 1163 Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders Paris Descartes \u2013 Sorbonne Paris Cit\u00e9 University, Imagine Institute, Necker\u2010Enfants Malades Hospital 75015 Paris France"},{"name":"Service de Radiologie P\u00e9diatrique, H\u00f4pital Necker\u2010Enfants Malades AP\u2010HP 75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Munnich","sequence":"additional","affiliation":[{"name":"INSERM UMR 1163 Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders Paris Descartes \u2013 Sorbonne Paris Cit\u00e9 University, Imagine Institute, Necker\u2010Enfants Malades Hospital 75015 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia M. 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