Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort

Table 2 Disorder of sex development patient cohort and variant summary

Cohort					DSD gene variants		Variant classification (number of patients)
Classification		Trios/duos	Singletons	Total	Patients with no DSD variant	Patients with curated variant	Pathogenic	Likely pathogenic	VUS
46,XY DSD
(A) Disorders of gonadal (testicular) development
46,XY	Complete gonadal dysgenesis (CGD)	3	21	24	11	13	6	7	0
46,XY	Partial gonadal dysgenesis (PGD)	2	19	21	13	8	2	4	2
46,XY	Ovo-testicular DSD (OT)	3	3	6	4	2	1	1	0
46,XY	Gonadal regression (GR)	0	1	1	1	0	0	0	0
				52	29	23	Genetic diagnosis = 21 (40%)
(B) Disorders in androgen synthesis or action
46,XY	Suspected androgen syn/action disorder (DASA)	12	23	35	11	24	18	2	4
46,XY	Leydig cell hypoplasia (LCH)	0	1	1	0	1	0	1	0
46,XY	Persistent mullerian duct syndrome (PMDS)	1	0	1	0	1	1	0	0
				37	11	26	Genetic diagnosis = 22 (60%)
(C) Other
46,XY	Hypospadias	12	34	46	20	26	6	10	10
46,XY	Syndromic	5	4	9	6	3	1	1	1
46,XY	Diphallus	0	1	1	1	0	0	0	0
				56	27	29	Genetic diagnosis = 18 (32%)
(D) Unknown
46,XY	DSD (origin unknown)	25	108	133	52	81	41	16	24
							Genetic diagnosis = 57 (43%)
Total 46,XY DSD		63	215	278	119	159	76	42	41
							Genetic diagnosis = 118 (43%)
46,XX DSD
(A) Disorders of gonadal (ovarian) development
46,XX	Testicular DSD	2	14	16	8	8	8	0	0
46,XX	Ovotesticular DSD	2	5	7	6	1	0	0	1
46,XX	Gonadal dysgenesis (GD)	2	1	3	3	0	0	0	0
				26	17	9	Genetic diagnosis = 8 (31%)
(B) Androgen excess				0
(C) Other
46,XX	MRKH	0	9	9	9	0	0	0	0
46,XX	Dysplastic ovaries	1	0	1	1	0	0	0	0
46,XX	Syndromic	1	1	2	2	0	0	0	0
				12	12	0
(D) Unknown
46,XX	DSD (origin unknown)	4	6	10	10	0	0	0	0
Total 46,XX DSD		12	36	48	39	9	8	0	1
							Genetic diagnosis = 8 (17%)
Total all DSD		75	251	326	158	168	84	42	42

Patients have been categorized based on clinical notes provided, according to the recommended classification of DSD in the Chicago Consensus report [1]. The number of singleton and patients with family members (duos or trios) are shown for each DSD. Given the difficulty of classifying some DSD patients, we have included an “unknown” category for 46,XY undervirilized patients and 46,XX virilized patients with unknown cause. This table also lists the numbers of patients in each DSD classification with a variant in a clinically relevant DSD gene. This is shown as a total number and broken down into variant classifications: pathogenic, likely pathogenic, and variants of uncertain significance (VUS). Variants which are classified as pathogenic or likely pathogenic are considered to be a genetic diagnosis and have been indicated for each phenotypic category. In cases where a patient had variants in multiple genes, the variant with the highest classification (pathogenic > likely pathogenic > VUS) was taken into consideration for this chart. The exact variants in each patient can be found in Additional file 1: Table S1. Entries in bold are subtotals and totals. MRKH Mayer-Rokitansky-Küster-Hauser syndrome

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