46,XY disorder of sex development and developmental delay associated with a novel 9q33.3 microdeletion encompassing NR5A1.
Steroidogenic factor 1 (SF1) is a nuclear receptor encoded by the NR5A1 gene. SF1 affects both sexual and adrenal development through the regulation of target gene expression. Genotypic male and female SF1 knockout mice have adrenal and gonadal agenesis with persistent Müllerian structures and early lethality. There have been several reports of NR5A1 mutations in individuals with 46,XY complete gonadal dysgenesis (CGD) or other disorders of sex development (DSD) with or without an adrenal phenotype. To date microdeletions involving NR5A1 have been reported in only two patients with DSDs. We report a novel microdeletion encompassing NR5A1 in a patient with 46,XY DSD and developmental delay. The phenotypically female patient initially presented with mild developmental delay and dysmorphisms. Chromosome analysis revealed a 46,XY karyotype. A 1.54 Mb microdeletion of chromosome 9q33.3 including NR5A1 was detected by array CGH and confirmed by FISH. Normal maternal FISH results indicated that this was most likely a de novo event. Since most NR5A1 mutations have been ascertained through gonadal or adrenal abnormalities, the additional findings of developmental delay and minor facial dysmorphisms are possibly related to haploinsufficiency of other genes within the 1.54 Mb deleted region. This report further confirms the role of NR5A1 deletions in 46,XY DSD and reinforces the utility of aCGH in the work up of DSDs of unclear etiology.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: tracy.brandt@mssm.edu.
Tracy
T
Brandt
Leah
L
Blanchard
Khyati
K
Desai
Saroj
S
Nimkarn
Ninette
N
Cohen
Lisa
L
Edelmann
Lakshmi
L
Mehta
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D058490:Disorder of Sex Development, 46,XY / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D059785:Karyotype; D054339:Steroidogenic Factor 1 / Q000235:genetics*; D013577:Syndrome
C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1
46,XY DSD; 46,XY disorder of sex development; 9q33 Microdeletion; NR5A1; SF1