Clinical and molecular spectrum of 46,XY disorders of sex development that harbour MAMLD1 variations: case series and review of literature

Table 1 Clinical findings, endocrine parameters and genetic results of the 10 Chinese 46, XY patients with MAMLD1 variants

Patient	Visit Age	Phenotype				Serum hormone values							*MAMLD1* variants
Patient	Visit Age	Hypos- padias	Micro- penis	Crytor- chidism	Urethral Meatus	LH, IU/L	FSH, IU/L	T/T after HCG, ng/dl	INHB, pg/ml^a	AMH, ng/ml	ACTH, pg/ml	Cortisol, μg/dl	Nucleotide Change	Amino AcidChange	Variant Type	ACMG
1	1.3 yr	+	+	–	Penoscrotal	<0.10	1.14	<20.0/257	158	>23	32.9	9.57	c.1986C>G	p.S662R	Missense	VUS
2	4 mo	+	+	–	Scrotal	0.16	0.18	<20.0/564.0	NA	NA	50.5	14.8	c.1066C>T	p.R356X	Nonsense	P
3	4 mo	+	+	–	Scrotal	6.63	3.16	30.9/744	123.8	>23	305/35.7	23.1	c.1066C>T	p.R356X	Nonsense	P
4	2.25 yr	Penis enlargement; Premature puberty			Normal	16.86^b/0.3^c/13.6^d	6.78^b/0.78^c/10.7^d	36.43^b/<20.0^c	237.64	>23	33.9^c	7.58^c/37.6^e	c.1261G>C	p.A421P	Missense	VUS
5	3 mo	+	+	–	Subcoronal	6.45	3.66	163	89.5	>23	24.9	10.5	c.454C>T	p.Q152X	Nonsense	P
6	3 mo	+	+	+	Penoscrotal	0.189	4.7	<20.0/257.9	128.83	122	88.12/17.0^f	10.2/13.50^f	c.1624C>T	p.P542S	Missense	LB
7	3 yr	+	+	+	Perineal	<0.10	3.97	<20.0/89.45	NA	NA	43.6	10.7	c.1000C > T	p.P334S	Missense	LP
8	3 mo	+	–	–	Perineal	1.27	1.32	77.3/435	291.91	>23	120	6.18	c.370C > T	p.Q124X	Nonsense	P
9	2.5 yr	–	+	–	Normal	<0.10	0.59	135	125.3/309	>23	38.7	7.4	c.2975C>T	p.T992I	Missense	VUS
10	1 yr	+	–	+	Perineal	0.16	0.74	<20.0	NA	NA	NA	NA	c.2780G>T	p.R927L	Missense	LB
Overall		8/10	7/10	3/10

+, Positive Phenotype; −, Negative Phenotype; NA Data non-available, LH Luteinizing hormone, FSH Follicle stimulating hormone, T Testosterone, AMH anti-Müllerian hormone, ACTH Adrenocorticotropic hormone; ^a indicating the normal reference range for Inhibin-B, that is 75–350 normal sperm production, 50–80 suspicious spermatogenesis disturbance, <50 spermatogenesis disturbance; ^b indicating the parameters were measured at age of 1 years old; ^c indicating the parameters were measured at age of 1 year and 10 months; ^d indicating the peak value of parameters after gonadotropin hormone releasing hormone (GnRH) stimulated test at age of 2 year and 3 months; ^e indicating the peak value of parameters after ACTH stimulated test at age of 2 year and 3 months; ^f indicating the parameters were measured at age of 9 months; ACMG the American College of Medical Genetics and Genomics, VUS Uncertain Significance, P Pathogenic, LB Likely Benign, LP Likely Pathogenic

ISSN: 1750-1172