Deletion 9p and sex reversal.

Abstract

We report a case of a female infant with a de novo deletion of the short arm of chromosome 9, sex reversal, and an apparently intact SRY gene. Sex reversal has been reported in a number of subjects with a normal Y chromosome and a deletion of the terminal segment of the short arm of chromosome 9. The factors controlling early development of the male testes are unknown. There are likely to be many genes involved and we present additional evidence that one of these is situated on the end of the short arm of chromosome 9. (J Med Genet 1993;30:518-20) The primary event in the determination of male and female sex is dependent on the presence or absence of the sex determining region of the Y chromosome (SRY).1 Sex reversal has been reported in a number of subjects with a Y chromosome and a terminal deletion of the short arm of chromosome 9.2-6 These cases involved translocation of chromosome 9 with other chromosomes and therefore they were trisomic for part of another chromosome in addition to being monosomic for terminal 9p. We report a case of a sex reversed female infant with a de novo deletion of the distal short arm of chromosome 9, sex reversal, and an apparently intact SRY gene. Figure 1 Partial G banded metaphase to show deleted chromosome 9 with apparently terminal deletion of the short arm del (9) (p2305). Frozen fibroblasts from the proband are banked at Guy's Hospital, reference 90/3077.The SRY gene was amplified by the polymerase chain reaction, cloned, and sequenced and no mutations found.' Endocrine investigations Endocrine investigation was consistent with gonadal failure with a raised FSH of > 40 mU/l (normal range < 2 mU/l). The LH rose markedly after LHRH stimulation from 11 IU/l to > 50 IU/l (resting normal range 1-6 IU/1). The testosterone rose only minimally from 0*9 to 1-5 nmol/l (resting normal range A1Onmol/l) after three injections of HCG (1000 units x 3).~~- Docherty, Robb, Ramani, Hawkins, Grant Summary of patients with sex reversal and deletions of the distal short arm of chromosome 9.

Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation

“…DM domain genes have been implicated in vertebrate sexual development by chromosomal location and by embryonic expression. Human DMRT1 maps to an autosomal locus (9p24.3) that, when hemizygous, is associated with defective testicular development and consequent 46,XY feminization (Crocker et al 1988;Hoo et al 1989;Bennett et al 1993;Veitia et al 1997Veitia et al , 1998Flejter et al 1998;Guioli et al 1998;Raymond et al 1998). In birds, which have ZZ/ZW sex determination, Dmrt1 is found on the Z chromosome (Nanda et al 1999), again suggesting that two doses of Dmrt1 (ZZ=male) might be necessary for testis development.…”

A Case of Partial Short Arm Deletion in Chromosome 9 with Inguinal Hernia, Testicular Cystic Lesion, and Arthrogryposis Multiplex Congenita

“…In addition, our patient showed symptoms of AMC, which have not previously been reported in patients with de novo 9p deletion syndrome. Various studies have reported that 9p deletion syndrome is caused by a partial monosomy of 9p, with breakpoint sites mainly in the regions 9p22 to 9p24 5) .…”

“…DMRT1 activates testis specific genes such as Sox9 and Sox8, and represses ovary specific genes encoding Fox12, Wnt4 and R spondin 1 signaling proteins, and estrogen receptors 2,5,7) . CER1…”

“…Patients who have the 9p deletion as well as the 46, XY chromosomal disorder have shown abnormal sexual development 5,6) .…”

O enigma da determinação gonadal: o que existe além do cromossomo Y?

“…Em 70% dos pacientes 46,XY, estão presentes órgãos genitais anormais e seis casos extremos de reversão sexual foram publicados (38). Rossodivita e col. relatam dois casos de alterações no cromossomo 9 com hipogonadismo secundário e grave insuficiência testicular (39). A disfunção testicular nestes casos poderia estar relacionada às fases iniciais da determinação sexual, cujos fatores controladores ainda não são bem conhecidos.…”