Renpenning Syndrome Maps to Xp11

Abstract

Mutations in genes on the X chromosome are believed to be responsible for the excess of males among individuals with mental retardation. Such genes are numerous, certainly >100, and cause both syndromal and nonsyndromal types of mental retardation. Clinical and molecular studies have been conducted on the Mennonite family with X-linked mental retardation (XLMR) reported, in 1962, by Renpenning et al. The clinical phenotype includes severe mental retardation, microcephaly, up-slanting palpebral fissures, small testes, and stature shorter than that of nonaffected males. Major malformations, neuromuscular abnormalities, and behavioral disturbances were not seen. Longevity is not impaired. Carrier females do not show heterozygote manifestations. The syndrome maps to Xp11.2-p11.4, with a maximum LOD score of 3.21 (recombination fraction 0) for markers between DXS1039 and DXS1068. Renpenning syndrome (also known as "MRXS8"; gene RENS1, MIM 309500) shares phenotypic manifestations with several other XLMR syndromes, notably the Sutherland-Haan syndrome. In none of these entities has the responsible gene been isolated; hence, the possibility that two or more of them may be allelic cannot be excluded at present.

Identification and Characterization of proSAAS, a Granin-Like Neuroendocrine Peptide Precursor that Inhibits Prohormone Processing

“…The genomic position of human proSAAS on chromosome X maps within regions associated with several different X-linked mental retardation syndromes (Gedeon et al, 1994;Stevenson et al, 1998). In addition, a susceptibility haplotype for insulindependent diabetes mellitus has been mapped to chromosome Xp13-11, which contains the proSAAS locus (Cucca et al, 1998).…”

Mapping of a gene (MRXS9) for X-linked mental retardation, microcephaly, and variably short stature to Xq12-q21.31

“…The original family with Renpenning syndrome (RENS1, MRXS8) was mapped to Xp11 [Stevenson et al, 1998]. Thus it would appear that, since the two critical regions of the present family and the original Renpenning family do not overlap, these are two separate entities and that there is locus heterogeneity for Renpenning-type syndrome, and the gene for the current disease has been given the designation MRXS9.…”

X-linked mental retardation with variable stature, head circumference, and testicular volume linked to Xq12-q21

“…They usually had severe mental impairment. The Renpenning syndrome has been mapped to Xp11.2-p11.4, excluding the possibility that the family reported here is the same as Renpenning syndrome [Stevenson et al, 1998]. Table III lists those X-linked entities with mental retardation and small head size, short stature, or small testicular volume that either map to the same region as our entity or whose localization is not presently known.…”