New insights into molecular diagnosis of some genetic disorders characterized by short stature

In the last decade, a progressively increasing number of genetic factors have proved to be involved in the pathogenesis of growth disorders. This report gives an overview of the involvement of short stature homeoboX-containing gene (SHOX), protein-tyrosine phosphatase nonreceptor-type 11 gene (PTPN11), microcephalin gene (MCHP1), plant homeodomain (PHD)-like finger gene (PHF6) and lamin A (LMNA) gene in syndromic conditions characterized by short stature. SHOX gene encodes a transcription factor implicated in the cell cycle and bone growth. A remarkable phenotypic heterogeneity has been observed in syndromes related to SHOX mutations, ranging from severe features to isolated short stature. PTPN11 gene encodes SHP-2 phosphatase, one of the intermediates of intracellular growth signalling. Of particular interest is the relationship between the constitutive activation of mutated SHP-2 protein and short stature, hyporesponder also to exogenous GH. MCPH1 and PHF6 genes have recently been described to be mutated in syndromes characterized by microcephaly and short stature. The former gene encodes a protein involved in the control of cell cycle and chromosome condensation apparatus, the latter one encodes a novel zinc finger protein of unknown function. Finally, we report the literature data on the LMNA gene and on the new perspective for genetic correction of premature aging phenotype in Hutchinson-Gilford progeria syndrome.