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Mendeliome v1.4739 EMX2 Krithika Murali changed review comment from: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs that included 18 genes in the minimal critical region including EMX2 in individuals with DSD and developmental delay. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence; to: PMID: 25577462 Lin et al 2014 - novel, heterozygous EMX2 PTC variant (p.E142X) identified in an XX female with didelphic uterus, variant inheritance unknown. Western blot and functional studies indicated formation of a truncated protein with dominant-negative effect. Variant was identified through direct sequencing of EMX2 in a cohort of 517 patients with incomplete Mullerian fusion.

PMID: 33434492 Chen et al 2021 AJHG, identified a novel, heterozygous EMX2 PTC variant (p.Tyr120ter) in a female with type I MKHS (inheritance unknown). Identified through exome-sequencing in an MKHS cohort.

PMID: 34829455 Miclea et al 2021 (Diagnostic) - large panel sequencing performed in a DSD cohort. Novel missense (inheritance unknown) - p.Arg205Gln - identified in a 4 yo XY male with hypospadius, GDD/ID, Pierre-robin sequence, hydrocephalus. Variant located in the DNA binding domain, classified as VUS.

PMID: 41765865 Stamou et al 2026 (Genetics in Medicine) performed trio WES on an idiopathic hypogonadotrophic hypogonadism cohort. 3 de novo CNVs detected in individuals with DSD and developmental delay - 18 genes including EMX2 in the minimal critical region. In addition, x2 unrelated individuals with DSD, dev delay, hearing loss had a heterozygous de novo p.Lys199Gln missense variant located in the DNA binding domain. x1 individual identified with crytorchidism and a heterozygous Ser111Ter variant (inheritance unknown).

Based on the current evidence:
- Green for hypogonadotrophic hypogonadism and DSD
- Amber for ID - based on 3 unrelated individuals with dev delay and variants in the DNA binding domain (p.Arg205Gln, p.Lys199Gln)
- Red for Pierre-Robin sequence
Mendeliome v1.4739 EMX2 Krithika Murali Phenotypes for gene: EMX2 were changed from Schizencephaly, MIM# 269160 to Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related; DSD, EMX2-related
Mendeliome v1.4738 EMX2 Krithika Murali Publications for gene: EMX2 were set to 8528262; 9359037; 9153481; 9153481; 18409201
Mendeliome v1.4737 EMX2 Krithika Murali Classified gene: EMX2 as Green List (high evidence)
Mendeliome v1.4737 EMX2 Krithika Murali Gene: emx2 has been classified as Green List (High Evidence).
Mendeliome v1.4736 EMX2 Krithika Murali reviewed gene: EMX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 41765865, 34829455, 33434492, 25577462; Phenotypes: Hypogonadotropic hypogonadism, MONDO:0015770, EMX2-related, 46,XX or XY DSD, EMX2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.3804 EMX2 Zornitza Stark edited their review of gene: EMX2: Changed rating: RED
Mendeliome v1.3804 EMX2 Zornitza Stark Classified gene: EMX2 as Red List (low evidence)
Mendeliome v1.3804 EMX2 Zornitza Stark Gene: emx2 has been classified as Red List (Low Evidence).
Mendeliome v0.2655 EMX2 Zornitza Stark Tag disputed tag was added to gene: EMX2.
Mendeliome v0.2655 EMX2 Zornitza Stark Marked gene: EMX2 as ready
Mendeliome v0.2655 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2655 EMX2 Zornitza Stark Phenotypes for gene: EMX2 were changed from to Schizencephaly, MIM# 269160
Mendeliome v0.2654 EMX2 Zornitza Stark Publications for gene: EMX2 were set to
Mendeliome v0.2653 EMX2 Zornitza Stark Mode of inheritance for gene: EMX2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2652 EMX2 Zornitza Stark Classified gene: EMX2 as Amber List (moderate evidence)
Mendeliome v0.2652 EMX2 Zornitza Stark Gene: emx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2651 EMX2 Zornitza Stark reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 8528262, 9359037, 9153481, 9153481, 18409201; Phenotypes: Schizencephaly, MIM# 269160; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.0 EMX2 Zornitza Stark gene: EMX2 was added
gene: EMX2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EMX2 was set to Unknown