Table 1.
Clinical and Hormonal Features of 12 Patients with Central Precocious Puberty and MKRN3 Mutations in Five Families.*
| Patient No. | Sex | MKRN3 Mutation | Initial Clinical Presentation | Time of Diagnosis | LH† | FSH† | Estradiol† | Testosterone† | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DNA | Protein | Condition | Age | Age | Tanner Stage | Bone Age | Basal | After GnRH Stimulation | Basal | After GnRH Stimulation | ||||
|
|
|
|
|
|
||||||||||
| yr | yr | yr | IU/liter | IU/liter | pg/ml | ng/dl | ||||||||
| Family A | ||||||||||||||
| III-1 | Female | 637delC | Arg213Glyfs*73 | Thelarche | 5.7 | 6.5 | 2 | 7.7 | 0.8 | 13.6 | 3.8 | — | 25 | — |
| III-2 | Male | 637delC | Arg213Glyfs*73 | Testicular enlargement | 8.0 | 8.7 | 3 | 11.0 | 2.9 | 20.0 | 2.5 | — | — | 78 |
| III-3 | Female | 637delC | Arg213Glyfs*73 | Thelarche | 6.5 | 6.7 | 2 | 7.8 | 1.1 | 16.7 | 4.5 | — | <15 | — |
| Family B | ||||||||||||||
| III-1 | Female | 1171_1172insA | Tyr391* | Thelarche | 6.2 | 7.0 | 3 | 7.0 | <0.6 | 36.0 | 1.13 | 17.9 | 13.2 | — |
| III-2 | Female | 1171_1172insA | Tyr391* | Thelarche | 5.7 | 6.0 | 3 | 6.0 | <0.6 | 37.3 | 1.13 | 27.9 | 11 | — |
| Family C | ||||||||||||||
| III-1 | Female | 1095G→T | Arg365Ser | Thelarche | 6.2 | 6.4 | 2 | 9.4‡ | <0.1 | 7.3 | 7 | 7.3 | 49 | — |
| III-2 | Male | 1095G→T | Arg365Ser | Testicular enlargement and pubarche | Unknown | 9.7 | 3 | 12.0 | 2.0 | 19.5 | 4.4 | 19.5 | — | 67 |
| III-3 | Female | 1095G→T | Arg365Ser | Thelarche and pubarche | 5.4 | 5.7 | 2 | 8.5 | 0.5 | 12.3 | 3.6 | 14.5 | <15 | — |
| Family D | ||||||||||||||
| III-2 | Male | 475_476insC | Ala162Glyfs*14 | Testicular enlargement and pubarche | 5.9 | 8.1 | 3 | 10.0 | 1.18 | 6.7 | 1.53 | 2.6 | — | 116 |
| III-3 | Male | 475_476insC | Ala162Glyfs*14 | Testicular enlargement and pubarche | Unknown | 9.7 | 3 | 9.7 | 1.6 | 10.9 | 0.8 | 2.6 | — | 548 |
| Family E | ||||||||||||||
| III-1 | Male | 475_476insC | Ala162Glyfs*14 | Testicular enlargement and pubarche | 8.5 | 8.8 | 3 | 11.5 | 4.1 | — | 3.1 | — | — | 216 |
| III-2 | Female | 475_476insC | Ala162Glyfs*14 | Thelarche | 5.0 | 6.5 | 2 | 8.3 | — | 7.4 | 13 | — | 13 | — |
The available information on family ancestry is as follows: Family A reported Northwest European ancestry (from Wales, living in the United States); Family B reported living in Brazil, but their ancestry was not reported; Family C reported Northwest European ancestry (from Belgium and living in Belgium); Family D reported living in Brazil, but their ancestry was not reported; and Family E reported European ancestry (the ancestry of the proband’s father is Italian, and the mother reported European ancestry; specific details of the mother’s country of origin in Europe are not available). FSH denotes follicle-stimulating hormone, and LH luteinizing hormone. Dashes indicate that data are not available.
Normal prepubertal levels of testosterone and estradiol are less than 12.0 ng per deciliter and less than 15.0 pg per milliliter, respectively; the normal prepubertal basal level of LH is less than 0.15 IU per liter, with a peak level below 5.0 IU per liter in both girls and boys. Levels were measured at the time of diagnosis. Normal pubertal levels of FSH have not been established because the normal ranges for pubertal and prepubertal FSH overlap.
This was the patient’s bone age when she was 7.4 years old.