Table 1. Clinical Presentation of Four Patients with Mutations in PNLDC1.^*.

Variable	Patient 1†	Patient 2	Patient 3	Patient 4
Genetics
PNLDC1 mutation	Homozygous nonsense	Homozygous missense	Compound heterozygous frameshift and missense	Homozygous splice acceptor variant
Karyotype	46,XY	46,XY	46,XY	46,XY
Y chromosome microdeletions	No	No	No	No
Patient history
Age — yr	32	42	39	36
Ethnic origin‡	Pakistani	Qatari	Unknown	Emirati
Congenital maldescended testicles	No	No	Unknown	No
Pubertal development	Normal	Normal	Unknown	Normal
Psychiatric diagnosis	Schizophrenia	Normal	Unknown	Normal
Phenotype
Body-mass index§	30	26	Unknown	20
Gynecomastia	No	No	Unknown	No
Pubic hair growth — Tanner stage¶	6	6	Unknown	Unknown
Hypospadias	No	No	No	No
Left/right testis position in scrotum	Low/low	Low/low	Low/low	Low/low
Left/right testis size — ml	15/12‖	10.9/13.0**	Unknown	10/10‖
Epididymis	Bilateral present; not enlarged	Bilateral present; not enlarged	Bilateral present; not enlarged	Bilateral present; not enlarged
Results of transrectal ultrasonography	Prostate normal; ejaculatory ducts normal	Unknown	Prostate normal; ejaculatory ducts normal	—
Semen characteristics
Ejaculation abstinence — days	3	3	Unknown	2
Semen volume — ml	1.3–1.5	3	Unknown	2.3
Sperm concentration	Azoospermia	Azoospermia	Azoospermia	Azoospermia
Spermatozoa in ejaculate pellet	None	None	None	None
Semen pH	8.5	Alkaline	Unknown	8.0
Hormone levels
Serum total testosterone — nmol/liter	6–12	12	16	18
Serum free testosterone — nmol/liter	0.14–0.31	0.32	Unknown	Unknown
Serum SHBG — nmol/liter	21–23	19	Unknown	Unknown
Serum FSH — IU/liter	4.7–4.9	4.4	7.4	4.8
Serum LH — IU/liter	3.4–4.3	7.0	6.0	Unknown
Serum inhibin B — pg/ml	151–157	55	Unknown	Unknown
Serum estradiol — pmol/liter	39–49	73	115	Unknown
Testicular-biopsy sample
Fixative	Modified Stieve’s fixative	Bouin’s fixative	Unknown	Formalin
Leydig cell hyperplasia	No	No	Unknown	No
Spermatogenesis	Bilateral homogenous pattern with spermatogenic arrest at the late pachytene stage	Homogenous pattern with spermatogenic arrest at the late pachytene stage	No biopsy available (only tissue remnants after TESE were available)	Homogenous pattern with spermatogenic arrest at the late pachytene stage
RNA recovered	Yes	No	Yes, from remnants after TESE	Yes
Treatments
TESE or microTESE	Unknown	No sperm identified after extensive TESE	TESE revealed morphologically abnormal spermatozoa	No sperm identified after extensive TESE
Treatment outcome	Unknown	No pregnancy	No pregnancy after ICSI with abnormal spermatozoa obtained from TESE	No pregnancy

^*Patient 1 was from Denmark, Patient 2 from the United States, Patient 3 from Portugal, and Patient 4 from the Netherlands. To convert the values for estradiol to picograms per milliliter, divide by 3.671. To convert the values for testosterone to nanograms per milliliter, divide by 3.467. FSH denotes follicle-stimulating hormone, ICSI intracytoplasmic sperm injection, LH luteinizing hormone, SHBG sex hormone–binding globulin, and TESE testicular sperm extraction.

^†The reproductive hormones in Patient 1 were measured in several samples, and the range is indicated.

^‡Information on ethnic origin was obtained from the medical records of the patients. The ethnic origin of Patient 3 was unknown, although he had an Arabic name.

^§The body-mass index is the weight in kilograms divided by the square of the height in meters.

^¶Tanner stages of pubic hair range from 1 to 6, with higher stages indicating more advanced pubertal development.

^‖Testis size was determined by palpation.

^**Testis size was determined by ultrasonograpy.