PMID- 37551848
OWN - NLM
STAT- MEDLINE
DCOM- 20231114
LR  - 20231116
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Linking)
VI  - 191
IP  - 12
DP  - 2023 Dec
TI  - The smallest likely pathogenic duplication of a SOX9 enhancer identified to date 
      in a family with 46,XX testicular differences of sex development.
PG  - 2831-2836
LID - 10.1002/ajmg.a.63367 [doi]
AB  - Copy number variants that duplicate distal upstream enhancer elements of the SOX9 
      gene cause 46,XX testicular differences of sex development (DSD) which is 
      characterized by a 46,XX karyotype in an individual presenting with either 
      ambiguous genitalia or genitalia with varying degrees of virilization, including 
      those resembling typical male genitalia. Reported duplications in this region 
      range in size from 24 to 780 kilobases (kb). Here we report a family with two 
      affected individuals, the proband and his maternal uncle, harboring a 3.7 kb 
      duplication of a SOX9 enhancer identified by clinical genome sequencing. Prior 
      fluorescence in situ hybridization (FISH) for SRY and a multi-gene panel for 
      ambiguous genitalia were non-diagnostic. The unaffected mother also carries this 
      duplication, consistent with previously described incomplete penetrance. To our 
      knowledge, this is the smallest duplication identified to-date, most of which 
      resides in a 5.2 kb region that has been previously shown to possess enhancer 
      activity that promotes the expression of SOX9. The duplication was confirmed by 
      quantitative-PCR and shown to be in tandem by bidirectional Sanger sequencing 
      breakpoint analysis. This finding highlights the importance of non-coding variant 
      interrogation in suspected genetic disorders.
CI  - (c) 2023 Wiley Periodicals LLC.
FAU - Sajan, Samin A
AU  - Sajan SA
AD  - lllumina Clinical Services Laboratory, Illumina Inc., San Diego, California, USA.
FAU - Brown, Carolyn M
AU  - Brown CM
AD  - lllumina Clinical Services Laboratory, Illumina Inc., San Diego, California, USA.
FAU - Davis-Keppen, Laura
AU  - Davis-Keppen L
AD  - USD Sanford School of Medicine, Sanford Children's Hospital, Sioux Falls, South 
      Dakota, USA.
FAU - Burns, Kaitlyn
AU  - Burns K
AD  - USD Sanford School of Medicine, Sanford Children's Hospital, Sioux Falls, South 
      Dakota, USA.
FAU - Royer, Erin
AU  - Royer E
AD  - USD Sanford School of Medicine, Sanford Children's Hospital, Sioux Falls, South 
      Dakota, USA.
FAU - Coleman, Jessica A Cooley
AU  - Coleman JAC
AD  - Greenwood Genetic Center, Greenwood, South Carolina, USA.
FAU - Hilton, Benjamin A
AU  - Hilton BA
AD  - Greenwood Genetic Center, Greenwood, South Carolina, USA.
FAU - DuPont, Barbara R
AU  - DuPont BR
AD  - Greenwood Genetic Center, Greenwood, South Carolina, USA.
FAU - Perry, Denise L
AU  - Perry DL
AD  - lllumina Clinical Services Laboratory, Illumina Inc., San Diego, California, USA.
FAU - Taft, Ryan J
AU  - Taft RJ
AD  - lllumina Clinical Services Laboratory, Illumina Inc., San Diego, California, USA.
FAU - Kesari, Akanchha
AU  - Kesari A
AD  - lllumina Clinical Services Laboratory, Illumina Inc., San Diego, California, USA.
LA  - eng
PT  - Case Reports
DEP - 20230808
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
RN  - 0 (SOX9 protein, human)
RN  - 0 (SOX9 Transcription Factor)
SB  - IM
MH  - Female
MH  - Humans
MH  - Male
MH  - In Situ Hybridization, Fluorescence
MH  - *Regulatory Sequences, Nucleic Acid
MH  - *Disorders of Sex Development/genetics
MH  - Mothers
MH  - Sexual Development
MH  - SOX9 Transcription Factor/genetics
OTO - NOTNLM
OT  - 46,XX testicular differences of sex development
OT  - SOX9
OT  - duplication
OT  - enhancer
EDAT- 2023/08/08 12:42
MHDA- 2023/11/14 06:43
CRDT- 2023/08/08 07:33
PHST- 2023/06/30 00:00 [revised]
PHST- 2023/05/24 00:00 [received]
PHST- 2023/07/28 00:00 [accepted]
PHST- 2023/11/14 06:43 [medline]
PHST- 2023/08/08 12:42 [pubmed]
PHST- 2023/08/08 07:33 [entrez]
AID - 10.1002/ajmg.a.63367 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2023 Dec;191(12):2831-2836. doi: 10.1002/ajmg.a.63367. Epub 
      2023 Aug 8.