{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T17:01:15Z","timestamp":1778432475889,"version":"3.51.4"},"reference-count":33,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2009,11,9]]},"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                     <jats:italic>IGF1R<\/jats:italic> (insulin-like growth factor 1 receptor) haploinsufficiency is a rare event causing difficulties in defining clear genotype\u2013phenotype correlations, although short stature is its well established hallmark. Several pure 15q26 monosomies (n=22) have been described in the literature, including those with breakpoints proximal to the <jats:italic>IGF1R<\/jats:italic> gene. Clinical heterogeneity is characteristic for these mainly de novo telomeric deletions and is illustrated by the involvement of several different organ systems such as the heart, diaphragm, lungs, kidneys and limbs, besides growth failure in the patient's phenotype. The clinical variability in these patients could be explained by the haploinsufficiency of multiple genes besides the <jats:italic>IGF1R<\/jats:italic> gene. In comparison, the six different <jats:italic>IGF1R<\/jats:italic> mutations revealed to date exhibit some variance in their clinical features as well, probably because different parts of the downstream <jats:italic>IGF1R<\/jats:italic> signalling cascade were affected.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Using the recently developed technique multiplex ligation dependent probe amplification (MLPA), a chromosome 15q26.3 microdeletion harbouring part of the <jats:italic>IGF1R<\/jats:italic> gene was identified in a Dutch family. This deletion segregated with short height in seven out of 14 relatives across three generations. Metaphase fluorescence in situ hybridisation (FISH) and Affymetrix 250k single nucleotide polymorphism (SNP) microarray were used to characterise the deletion into more detail and showed that exons 11\u201321 of the <jats:italic>IGF1R<\/jats:italic> and a small hypothetical protein (LOC 145814) were deleted.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Clinical work-up of this newly identified family, which constitutes the smallest (0.095\u2005Mb) pure 15q26.3 interstitial deletion to date, confirms that disruption of the <jats:italic>IGF1R<\/jats:italic> gene does not induce major organ malformation or severe mental retardation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2009.070730","type":"journal-article","created":{"date-parts":[[2009,12,2]],"date-time":"2009-12-02T23:07:45Z","timestamp":1259795265000},"page":"492-498","source":"Crossref","is-referenced-by-count":35,"title":["Phenotype\u2013genotype correlation in a familial <i>IGF1R<\/i> microdeletion case"],"prefix":"10.1136","volume":"47","author":[{"given":"D C M","family":"Veenma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H J","family":"Eussen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L C P","family":"Govaerts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S W K","family":"de Kort","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R J","family":"Odink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C H","family":"Wouters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A C S","family":"Hokken-Koelega","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"de Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2025100511270776000_47.7.492.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05329"},{"key":"2025100511270776000_47.7.492.2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1502"},{"key":"2025100511270776000_47.7.492.3","doi-asserted-by":"publisher","DOI":"10.1136\/mp.54.3.125"},{"key":"2025100511270776000_47.7.492.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(05)80084-4"},{"key":"2025100511270776000_47.7.492.5","doi-asserted-by":"publisher","DOI":"10.1210\/en.141.7.2557"},{"key":"2025100511270776000_47.7.492.6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021172"},{"key":"2025100511270776000_47.7.492.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(69)80224-6"},{"key":"2025100511270776000_47.7.492.8","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gnf056"},{"key":"2025100511270776000_47.7.492.9","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.161"},{"key":"2025100511270776000_47.7.492.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2006.10.006"},{"key":"2025100511270776000_47.7.492.11","unstructured":"Shaffer.Iscn 2005. 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