ORPHA: 500; DO: 0080549;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3p25.2 | LEOPARD syndrome 2 | 611554 | Autosomal dominant | 3 | RAF1 | 164760 |
A number sign (#) is used with this entry because of evidence that LEOPARD syndrome-2 (LPRD2) is caused by heterozygous mutation in the RAF1 gene (164760) on chromosome 3p25.
For a phenotypic description and a discussion of genetic heterogeneity of LEOPARD syndrome, see 151100.
Pandit et al. (2007) reported 2 women with LEOPARD syndrome-2. Both patients had short stature, hypertrophic cardiomyopathy, lentigines and cafe-au-lait spots, craniofacial anomlies including dolichocephaly, downslanting palpebral fissures, hypertelorism, thick lips, low-set ears with thickened helix, and prominent chin, short webbed nedk, cubitus valgus, and delayed puberty. One patient had mitral valve anomaly and the other had pulmonary valve stenosis.
The transmission pattern of LEOPARD syndrome-2 in the patients reported by Pandit et al. (2007) was consistent with autosomal dominant inheritance.
Pandit et al. (2007) analyzed the RAF1 gene in 6 individuals with LEOPARD syndrome who did not have mutations in the PTPN11 gene (176876) and identified 2 unrelated patients with heterozygous missense mutations (S257L, 164760.0001 and L613V, 164760.0004).
Pandit, B., Sarkozy, A., Pennacchio, L. A., Carta, C., Oishi, K., Martinelli, S., Pogna, E. A., Schackwitz, W., Ustaszewska, A., Landstrom, A., Bos, J. M., Ommen, S. R., and 17 others. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nature Genet. 39: 1007-1012, 2007. [PubMed: 17603483] [Full Text: https://doi.org/10.1038/ng2073]