TY - JOUR
T1 - Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene
AU - Digilio, Maria Cristina
AU - Conti, Emanuela
AU - Sarkozy, Anna
AU - Mingarelli, Rita
AU - Dottorini, Tania
AU - Marino, Bruno
AU - Pizzuti, Antonio
AU - Dallapiccola, Bruno
N1 - Funding Information:
The present study was supported, in part, by grants from the Italian Ministry of Health and Education. We thank Nicoletta Grifone, Caterina Tandoi, and Giorgia Esposito for technical support.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036074033&partnerID=8YFLogxK
U2 - 10.1086/341528
DO - 10.1086/341528
M3 - Article
C2 - 12058348
AN - SCOPUS:0036074033
SN - 0002-9297
VL - 71
SP - 389
EP - 394
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
M1 - 60483
ER -