Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene

Maria Cristina Digilio, Emanuela Conti, Anna Sarkozy, Rita Mingarelli, Tania Dottorini, Bruno Marino, Antonio Pizzuti, Bruno Dallapiccola

Research output: Journal PublicationArticlepeer-review

322 Citations (Scopus)


Multiple-lentigines (ML)/LEOPARD (multiple lentigines, electrocardiographic-conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness) syndrome is an autosomal dominant condition - characterized by lentigines and café au lait spots, facial anomalies, cardiac defects - that shares several clinical features with Noonan syndrome (NS). We screened nine patients with ML/LEOPARD syndrome (including a mother-daughter pair) and two children with NS who had multiple café au lait spots, for mutations in the NS gene, PTPN11, and found, in 10 of 11 patients, one of two new missense mutations, in exon 7 or exon 12. Both mutations affect the PTPN11 phosphotyrosine phosphatase domain, which is involved in <30% of the NS PTPN11 mutations. The study demonstrates that ML/LEOPARD syndrome and NS are allelic disorders. The detected mutations suggest that distinct molecular and pathogenetic mechanisms cause the peculiar cutaneous manifestations of the ML/LEOPARD-syndrome subtype of NS.

Original languageEnglish
Article number60483
Pages (from-to)389-394
Number of pages6
JournalAmerican Journal of Human Genetics
Issue number2
Publication statusPublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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