Cara Pengasuhan Anak Sebelum Ditegakkan Diagnosis Gangguan Perkembangan Sistem Reproduksi 46,XY

Latar belakang.Gangguan perkembangan sistem reproduksi 46,XY (GPSR 46,XY) bermanifestasi klinis beranekaragam, sehingga dapat dibesarkan sebagai anak laki-laki atau perempuan. Tujuan. Melihat sebaran cara pengasuhan individu dengan GPSR 46,XY dan dihubungkan dengan kemungkinan diagnosisnya. Metode.Penelitian deskriptif retrospektif dengan subyek GPSR yang dirujuk untuk analisis kromosom pada tahun 2009-2010 dan hasil analisis kromosom 46,XY. Hasil.Tujuh puluh pasien GPSR 46,XY dianalisis, dan ditemukan 45 dibesarkan sebagai laki-laki, 22 kasus dibesarkan sebagai perempuan, dan 3 kasus belum ditentukan cara pengasuhan jendernya. Sebagian besar pasien dirujuk pada usia antara >3 bulan-8 tahun, (32/70) pasien, dan 12 pasien dirujuk setelah usia 18 tahun. Alasan pasien dirujuk untuk analisis kromosom terutama adalah genitalia ambigu (44/70 kasus). Kesimpulan.Dengan pendekatan diagnosis yang tepat pada individu GPSR 46,XY orangtua dapat diarahkan untuk mengasuh jender yang sesuai. Untuk itu sangat diperlukan pemeriksaan klinis yang telit

Loss of DMRT1 gene in a Mos 45,XY,-9[8]/46,XY,r(9)[29]/47,XY,+idic r(9)× 2[1]/46,XY,idic r(9)[1]/46,XY[1] female presenting with short stature

Abstract Background A 46,XY sex reversal syndrome is characterized by discordant genetic and phenotypic sex, leading to normal external female genitalia, undeveloped gonads and presence of Müllerian structures in an otherwise 46,XY individual. Chromosome 9pter aberrations, such as ring chromosome have been reported to cause 46,XY disorders of sex development (DSD), due to involvement of DMRT1 gene located at the 9p24.3 region. Case presentation This study presents a unique case of a 12-year-old female with mos 46,XY, (r)9[31]/45,XY,-9[9] karyotype, presenting with intellectual disability and short stature, mimicking Turner syndrome. Re-karyotyping was performed using standard GTL-banding technique. Further cytogenetic study using standard metaphase fluorescent in situ hybridization (FISH) technique was applied to cultured lymphocytes from peripheral blood, hybridized using green control probe specific to 9q21 loci, and red DMRT1 probe specific to 9p24.3 loci. Cytogenetics and FISH analysis revealed mos 45,XY,-9[8]/46,XY,r(9)[29]/47,XY,+idic r(9)× 2[1]/46,XY,idic r(9)[1]/46,XY[1] and haploinsufficiency of DMRT1 gene in most cells. CGH array revealed a deletion around 1.25 Mb at 9p24.3 loci [arr 9p24.3(204,193-1,457,665)× 1] and three duplications around 13 Mb [9p24.3p22.3(1,477,660-14,506,754)× 3] near the breakage point that formed the ring chromosome 9. Conclusions The clinical presentation of the subject that mimics Turner syndrome highlights the importance of cytogenetic analysis to detect the possibility of ring chromosome 9. Sex reversal due to haploinsufficiency of DMRT1 gene in ring chromosome 9 structures is exceedingly rare with only a handful of cases ever reported. This finding further highlights the importance of DMRT1 gene in sex determination and differentiation in males. More research is required to pinpoint the exact mechanism that underlies sex reversal caused by DMRT1 haploinsufficiency

Diversity of sex chromosome abnormalities in a cohort of 95 Indonesian patients with monosomy X

Abstract Background Monosomy × or 45,X is a cytogenetic characteristic for Turner syndrome. This chromosome anomaly is encountered in around 50% of cases, but wide variations of other anomalies have been found. This report is to describe the cytogenetic characteristics of 45,X individuals. To the best of our knowledge, there were no large series of 45,X cases has been reported from Indonesia. Results Ninety five cases with 45,X cell line found, of which 60 were detected by karyotyping, 4 by FISH for sex chromosomes, and 31 by both karyotyping and FISH. Using karyotyping 37 out of 91 cases(40.6%) were identified as 45,X individuals, while cases who underwent FISH only 4 out of 35 cases (11.4%) showed 45,X result, resulting in total of 39 45,X cases (41.1%), and the rest 56 (58.9%) cases are mosaic. Among these cases, 21 out of 95 (22.1%) have Y or part of Y as the second or third sex chromosome in their additional cell lines. Result discrepancies revealed in 22 out of 31 cases who underwent both FISH and karyotyping, of which 7 showed normal 46,XX or 46,XY karyotypes, but by FISH, additional monosomy × cell line was found. Most of the cases were referred at the age of puberty (8-13 years old) or after that (14-18 years old), 31 and 21 cases respectively, and there were 14 cases were sent in adulthood. Conclusion Wide variations of sex chromosome aberrations have been detected using the combination of conventional cytogenetic and FISH, including detection of low level of mosaicism and Y-chromosome fragments. Result discrepancies using both techniques were found in 22/31 cases, and in order to obtain a more details of sex chromosome constitution of individuals with 45,X cell line both FISH and karyotyping should be carried out simultaneously.</p

Exceptional Complex Chromosomal Rearrangements in Three Generations

We report an exceptional complex chromosomal rearrangement (CCR) found in three individuals in a family that involves 4 chromosomes with 5 breakpoints. The CCR was ascertained in a phenotypically abnormal newborn with additional chromosomal material on the short arm of chromosome 4. Maternal karyotyping indicated that the mother carried an apparently balanced CCR involving chromosomes 4, 6, 11, and 18. Maternal transmission of the derivative chromosome 4 resulted in partial trisomy for chromosomes 6q and 18q and a partial monosomy of chromosome 4p in the proband. Further family studies found that the maternal grandmother carried the same apparently balanced CCR as the proband’s mother, which was confirmed using the whole chromosome painting (WCP) FISH. High resolution whole genome microarray analysis of DNA from the proband’s mother found no evidence for copy number imbalance in the vicinity of the CCR translocation breakpoints, or elsewhere in the genome, providing evidence that the mother’s and grandmother’s CCRs were balanced at a molecular level. This structural rearrangement can be categorized as an exceptional CCR due to its complexity and is a rare example of an exceptional CCR being transmitted in balanced and/or unbalanced form across three generations