These observations contribute to the phenotypic knowledge of patients with PQBP1 mutations and make this XLMR syndrome well recognizable to clinicians.
Thorough investigation of an MRX critical region in Xp22.1-21.3 enabled us to identify a new gene expressed in brain that is responsible for a non-specific form of X-linked mental retardation.
Renpenning syndrome (also known as "MRXS8"; gene RENS1, MIM 309500) shares phenotypic manifestations with several other XLMR syndromes, notably the Sutherland-Haan syndrome.
Here we report on the localization of a presumptive MRX gene to chromosomal region Xq24-q26 in a German family with nonspecific X-linked mental retardation (MRX 75, HUGO Human Gene Nomenclature Committee).
ATRX is a member of the Snf2 family of chromatin-remodelling proteins and is mutated in an X-linked mental retardation syndrome associated with alpha-thalassaemia (ATR-X syndrome).
Detailed comparison of the clinical characteristics and the function of the genes located in the commonly duplicated regions of these patients led us to the hypothesis that an increased dosage of ATRX and perhaps of other genes is involved in the pathogenetic mechanism of this XLMR phenotype, including mental retardation, short stature, and genital abnormalities comprising cryptorchidism and/or a small penis.
Mutation of the ATRX gene leads to X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome and several other X-linked mental retardation syndromes.
Detailed comparison of the clinical characteristics and the function of the genes located in the commonly duplicated regions of these patients led us to the hypothesis that an increased dosage of ATRX and perhaps of other genes is involved in the pathogenetic mechanism of this XLMR phenotype, including mental retardation, short stature, and genital abnormalities comprising cryptorchidism and/or a small penis.
In addition, OPHN-1 inactivation should be considered as a relevant model of developmental vermis disorganization, leading to a better understanding of the possible role of the cerebellum in MR.
Novel truncating mutations in the polyglutamine tract binding protein 1 gene (PQBP1) cause Renpenning syndrome and X-linked mental retardation in another family with microcephaly.
We report on a family with 4 affected males in 3 generations with a previously unreported X-linked mental retardation/multiple congenital anomaly (XLMR/MCA) syndrome.
Mutations in the polyglutamine tract binding protein 1 gene (PQBP1) have recently been reported in four XLMR disorders (Renpenning, Hamel cerebro-palato-cardiac, Sutherland-Haan, and Porteous syndromes) as well as in several other families.