Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene.
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.
Digilio
Maria Cristina
MC
Division of Medical Genetics, Bambino Gesù Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Conti
Emanuela
E
Sarkozy
Anna
A
Mingarelli
Rita
R
Dottorini
Tania
T
Marino
Bruno
B
Pizzuti
Antonio
A
Dallapiccola
Bruno
B
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D020125:Mutation, Missense; D009456:Neurofibromatosis 1 / Q000209:etiology / Q000235:genetics*; D009634:Noonan Syndrome / Q000209:etiology / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases