Abstract Ref Number = APCP848
MICRODELETION OF CHROMOSOME 15q11 IN A PATIENT WITH 46,XY SEX REVERSAL
Firman Prathama Idris,Shirley Renatha,Hannie Kartapradja,Chrysantine Paramayuda,Debby Ambarwati,Nanis Sacharina Marzuki,Jose RL Batubara
Eijkman Institute for Molecular Biology University of Indonesia
Background : Chromosome 15q11-q13 contains clusters of low copy repeat sequences called duplicons which could cause non-allelic homologous recombination due to meiotic misalignment. Deletion in this region causes Prader -Willi syndrome (PWS) and Angelman syndrome. Clinical presentation of PWS includes development delay, hypotonia, and infantile feeding problem. Furthermore, it could cause endocrine dysfunction such as hypogonadism with underdeveloped genital and/or pubertal development disorder. However, there is no report on PWS cases with severe undermasculinisation or sex reversal. Although advanced molecular tests are often used to analyse 46, XY Disorders of Development (DSD) patients, final etiologies may not be determined.
Case Presentation Summary : A 5 days-old female infant was referred due to genital ambiguity and macrocephaly (head circumference: 46.5 cm). Patient also showed micrognathia, high-arc palate, laryngomalacea, and CTEV (Congenital Talipes Equino Varus). Hormonal testing at 3 months revealed increased levels of FSH (133 mIU/mL), LH (13 mIU/mL), Testosterone (7.01 ng/dL) and Estradiol (21 pg/mL). MRI scan showed the presence of normally structured uterus and vagina with no detected testes. Normal 46,XY karyotype and normal SRY, SRD5A2, and AR gene sequences were revealed by cytogenetics and molecular analysis. Microarray analysis revealed a 1.9 Mb chromosome 15 microdeletion at q11.1-q11.2 loci [arr 15q11.1q11.2(20564608-22481028)×?1].
Learning Points/Discussion : The objective of this case report is to show the use of chromosomal microarray to analyse a dysmorphic 46,XY sex reversal patient with normal SRY, SRD5A2, and AR gene. Microarray analysis performed in our patient revealed a deletion at chromosome 15q11.1-q11.2, a region associated with PWS. This microdeletion encompasses region involved in PWS, however, it is inconclusive whether this deletion is associated with the sex reversal of the patient. Therefore, further molecular analysis is required to confirm this result.
Keywords: Microdeletion Chromosome 15q11 Disorders of Sex Development Microarray