PMID- 35164824
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220219
IS  - 1755-8166 (Print)
IS  - 1755-8166 (Electronic)
IS  - 1755-8166 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Feb 14
TI  - Identification of an SRY-negative 46,XX infertility male with a heterozygous 
      deletion downstream of SOX3 gene.
PG  - 2
LID - 10.1186/s13039-022-00580-7 [doi]
LID - 2
AB  - BACKGROUND: A male individual with a karyotype of 46,XX is very rare. We explored 
      the genetic aetiology of an infertility male with a kayrotype of 46,XX and SRY 
      negative. METHODS: The peripheral blood sample was collected from the patient and 
      subjected to a few genetic testing, including chromosomal karyotyping, 
      azoospermia factor (AZF) deletion, short tandem repeat (STR) analysis for AMELX, 
      AMELY and SRY, fluorescence in situ hybridization (FISH) with specific probes for 
      CSP 18/CSP X/CSP Y/SRY, chromosomal microarray analysis (CMA) for genomic copy 
      number variations(CNVs), whole-genome analysis(WGA) for genomic SNV&InDel 
      mutation, and X chromosome inactivation (XCI) analysis. RESULTS: The patient had 
      a karyotype of 46,XX. AZF analysis showed that he missed the AZF region 
      (including a, b and c) and SRY gene. STR assay revealed he possessed the AMELX in 
      the X chromosome, but he had no the AMELY and SRY in the Y chromosome. FISH 
      analysis with CSP X/CSP Y/SRY showed only two X centromeric signals, but none Y 
      chromosome and SRY. The above results of the karyotype, FISH and STR analysis did 
      not suggest a Y chromosome chimerism existed in the patient's peripheral blood. 
      The result of the CMA indicated a heterozygous deletion with an approximate size 
      of 867 kb in Xq27.1 (hg19: chrX: 138,612,879-139,480,163 bp), located at 104 kb 
      downstream of SOX3 gene, including F9, CXorf66, MCF2 and ATP11C. WGA also 
      displayed the above deletion fragment but did not present known pathogenic or 
      likely pathogenic SNV&InDel mutation responsible for sex determination and 
      development. XCI assay showed that he had about 75% of the X chromosome 
      inactivated. CONCLUSIONS: Although the pathogenicity of 46,XX male patients with 
      SRY negative remains unclear, SOX3 expression of the acquired function may be 
      associated with partial testis differentiation of these patients. Therefore, the 
      CNVs analysis of the SOX3 gene and its regulatory region should be performed 
      routinely for these patients.
CI  - (c) 2022. The Author(s).
FAU - Qin, Shengfang
AU  - Qin S
AUID- ORCID: 0000-0001-9391-890X
AD  - Department of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial 
      Maternity and Child Health Care Hospital, Chengdu, 610045, Sichuan, China. 
      qinshengfang@126.com.
FAU - Wang, Xueyan
AU  - Wang X
AD  - Department of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial 
      Maternity and Child Health Care Hospital, Chengdu, 610045, Sichuan, China.
FAU - Wang, Jin
AU  - Wang J
AD  - Department of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial 
      Maternity and Child Health Care Hospital, Chengdu, 610045, Sichuan, China.
LA  - eng
PT  - Journal Article
DEP - 20220214
PL  - England
TA  - Mol Cytogenet
JT  - Molecular cytogenetics
JID - 101317942
PMC - PMC8842887
OTO - NOTNLM
OT  - 46,XX male
OT  - Chromosome microarray chip
OT  - Fluorescence in situ hybridization
OT  - SRY-negative
OT  - Sex development and differentiation
OT  - Whole genome analysis
COIS- The authors declare that they have no competing interests.
EDAT- 2022/02/16 06:00
MHDA- 2022/02/16 06:01
PMCR- 2022/02/14
CRDT- 2022/02/15 05:31
PHST- 2021/10/24 00:00 [received]
PHST- 2022/01/28 00:00 [accepted]
PHST- 2022/02/15 05:31 [entrez]
PHST- 2022/02/16 06:00 [pubmed]
PHST- 2022/02/16 06:01 [medline]
PHST- 2022/02/14 00:00 [pmc-release]
AID - 10.1186/s13039-022-00580-7 [pii]
AID - 580 [pii]
AID - 10.1186/s13039-022-00580-7 [doi]
PST - epublish
SO  - Mol Cytogenet. 2022 Feb 14;15(1):2. doi: 10.1186/s13039-022-00580-7.