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Phenotypic and genotypic characterisation of Noonan-like/multiple giant cell lesion syndrome
  1. J S Lee1,
  2. M Tartaglia2,3,
  3. B D Gelb3,4,
  4. K Fridrich5,
  5. S Sachs6,
  6. C A Stratakis7,
  7. M Muenke8,
  8. P G Robey1,
  9. M T Collins1,
  10. A Slavotinek8,*
  1. 1Craniofacial and Skeletal Diseases Branch, NIDCR/NIH/DHHS, Bethesda, Maryland, USA
  2. 2Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanita, Rome, Italy
  3. 3Departments of Pediatrics, Mount Sinai School of Medicine, New York, USA
  4. 4Departments of Human Genetics, Mount Sinai School of Medicine, New York
  5. 5Department of Cell Biology (LHRRB), Harvard Medical School, Boston, Massachusetts, USA
  6. 6Department of Oral and Maxillofacial Surgery, State University of New York
  7. 7Developmental Endocrinology Branch, NICHD/NIH/DHHS
  8. 8Medical Genetics Branch, NHGRI/NIH/DHHS
  1. Correspondence to:
 Dr Janice S Lee
 Department of Oral and Maxillofacial Surgery, UCSF, 521 Parnassus Avenue C522, San Francisco, CA 94143-0440, USA; jsleeitsa.ucsf.edu

https://doi.org/10.1136/jmg.2004.024091

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    Noonan-like/multiple giant cell lesion syndrome (NL/MGCLS; OMIM 163955) is a rare condition1–3 with phenotypic overlap with Noonan’s syndrome (OMIM 163950) and cherubism (OMIM 118400) (table 1).

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    Table 1

     Comparison of the clinical characteristics of cherubism, Noonan’s syndrome, and Noonan-like/multiple giant cell lesion syndrome

    Recently, missense mutations in the PTPN11 gene on chromosome 12q24.1 have been identified as the cause of Noonan’s syndrome in 45% of familial and sporadic cases,4,5 indicating genetic heterogeneity within the syndrome. In the study by Tartaglia et al,5 there was a family in which three members had features of Noonan’s syndrome; two of these had incidental mandibular giant cell lesions.3 All three members were found to have a PTPN11 mutation known to cosegregate with the Noonan phenotype. This mutation, an A→G transition at position 923 in exon 8, predicting an Asn308Ser substitution within the PTP domain, was identified in an unrelated kindred with classical Noonan’s syndrome. No other patients with NL/MGCLS had been evaluated for the PTPN11 mutation.

    Cherubism is caused by a missense mutation in the coding region of the SH3BP2 gene on chromosome 4p16.3.6 In the study by Ueki et al,6 12 of 15 families showed point mutations in the SH3 binding protein, SH3BP2. All seven mutations identified were on exon 9 and affected three amino acids by substitution within a six amino acid sequence. A second locus or gene has not been identified.

    We present the phenotype of three sporadic cases of NS/MGCLS and the results of mutation analysis of the PTPN11 and SH3BP2 genes.

    CLINICAL REPORTS

    The clinical features of the three patients are summarised in table 2.

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    Table 2

     Phenotype of three patients with Noonan-like/multiple giant cell lesion syndrome

    All patients were enrolled in the National Institutes of Health IRB approved protocols and written informed consent was …

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    Footnotes

    • ↵* Current address: Department of Pediatrics, UCSF, San Francisco, California, USA

    • Conflicts of interest: none declared