| Title | Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene. | | Author(s) | Digilio MC, Conti E, Sarkozy A, Mingarelli R, Dottorini T, Marino B, Pizzuti A, Dallapiccola B | | Institution | Division of Medical Genetics, Bambino Gesù Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. | | Source | Am J Hum Genet 2002 Aug; 71(2):389-94. | | MeSH | Adolescent
Adult
Amino Acid Sequence
Child
Child, Preschool
Exons
Female
Humans
Intracellular Signaling Peptides and Proteins
Male
Mutation, Missense
Neurofibromatosis 1
Noonan Syndrome
Polymorphism, Single-Stranded Conformational
Protein Structure, Tertiary
Protein-Tyrosine-Phosphatase
Research Support, Non-U.S. Gov't
Sequence Analysis, DNA
| | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 12058348 |
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