Swyer Syndrome and 46,XY Partial Gonadal Dysgenesis Associated with 9p Deletions in the Absence of Monosomy-9p Syndrome

Abstract

Letters to the Editor 901 RCP mutations reported by Nathans et al. (1989) to cause reduced visual acuity but with normal fundus. In fact, figure 2 in the article by Nathans et al. (1989) shows a fundus photograph from a patient with "progressive bilateral central retinal degeneration" (p. 832). Other patients are described as having macular lesions and atrophy, on ophthalmic examination. Therefore, a phenotype such as the one Bergen and Pinckers observed in this family evidently could result from a mutation or combination of mutations in the red-and green-pigment genes. In these circumstances, exclusion of these genes is essential before a new locus is assigned.Bergen and Pinckers do indeed describe a multipoint analysis using markers DXS8103 and DXS8069, apparently spanning the RCP and GCP genes, that excludes these genes. However, this evidence is given as "data not shown," no LOD scores for these markers are included in table 3, and no reference is given to a published map proving that these markers span the genes in question. Furthermore, the authors' assertion that "Southern blot analysis with an RCP/GCP cDNA probe)did not reveal any structural abnormalities" (Bergen and Pinckers 1997, p. 1,472) surely is insufficient, since abnormalities at this locus can result from point mutations or from rearrangements 4-kb upstream of the red cone-pigment gene and 43-kb upstream of the green cone-pigment gene. Therefore, although data excluding the RCP/GCP locus in this family may exist, this could not be proved on the basis of the results presented.

FISH mapping of the sex-reversal region on human chromosome 9p in two XY females and in primates

“…[11][12][13][14][15][16] There is no correlation between the extent of sex reversal and the size of the del(9p). However, larger deletions leading to hemizygosity of many contiguous genes are associated with mental retardation and craniofacial abnormalities, in addition to partial or complete gonadal dysgenesis and ambiguous external and internal genitalia.…”

“…Deletion of the distal short arm of chromosome 9p21-24 is associated with failure of the testicular development and XY feminisation. [11][12][13] The critical region for XY sex reversal has been narrowed down to band 9p24.3 and contains two candidate genes, DMRT1 (doublesex and mab-3 related transcription factor 1, formerly named DMT1) and DMRT2, which are expressed in the adult testis. Both DMRT1 and DMRT2 contain a DNA-binding DM domain and share significant structural homology with male sexual regulatory genes from Caenorhabditis elegans (mab-3) and Drosophila melanogaster (dsx).…”

Novel DMRT1 3'UTR+11insT mutation associated to XY partial gonadal dysgenesis

“…It is well known that heterozygous small deletions in 9p can cause complete or partial XY gonadal dysgenesis (OMIM ID #154230) without other symptoms (9,10). A human gene located at 9p24.3 with sequence similarities to genes that regulate sexual development in insects and nematodes has been described as responsible for XY gonadal dysgenesis.…”

The ends of a continuum: genetic and temperature‐dependent sex determination in reptiles

“…Genes conserved across vertebrates that have been implicated in sex reversal, or that exhibit dose dependency, are obvious candidates. Dose deficiency in DMRT1 activity causes male-to-female sex reversal in humans (67) as does inactivation of SOX9. (68) Inactivation of WNT4 causes female-to-male sex reversal and its duplication causes male-to-female sex reversal, (69) though a similar function has not yet been demonstrated in reptiles.…”