Table 4.

Genotype-Phenotype Correlation in Cases 1–6 and Families A–F

Cases/Familiesa	Case 1	Families A and B	Case 2	Case 3b, Families C–F	Case 4	Case 5	Case 6
Molecular defects
Predicted mechanism for CYP19A1 overexpression	Duplication of CYP19A1 coding exons	Duplication of CYP19A1 promoters	Chimeric gene formation	Chimeric gene formation	Chimeric gene formation	Chimeric gene formation	Chimeric gene formation
Genes involved in chimeric gene formation	None	None	DMXL2	DMXL2	SEMA6D	TMOD3	CGNL1
Copy-number of the CYP19A1 exon 1.4c	Normal	Increased	Decreased	Normal	Increasedd	Normal	Decreased
Clinical findings
Onset of gynecomastia, y	7	10–13	Unknown	7–12	11	7	5
Gynecomastia (Tanner stage)	2–3	2–3	1–3e	3–5	3–4	Severe	Severe
Advanced bone age	Mild	Subtle	Moderate	Mild/ moderate	Severe	N.E.	N.E.

Abbreviation: N.E., not examined.

^aCases 1–6 were present cases, whereas families A–F were reported previously (5).

^bFine genomic structure of case 3 remains to be characterized.

^cExon 1.4 functions as the major promoter in extragonadal tissues.

^dDuplicated exon 1.4 has been disconnected from the coding exons of CYP19A1.

^eThe patient and his father had gynecomastia of Tanner stages 3 and 1, respectively.