Functional and Structural Consequences of Nine CYP21A2 Mutations Ranging from Very Mild to Severe Effects

Table 1

The genotypes and symptoms at diagnosis of the individuals carrying the novel mutations (marked in bold).

Subject number	Sex	Age at diagnosis	Symptoms	17OHP (nmol/liter); basal/stimulated	Genotype	Phenotype	Country of origin	Publication
1	F	4 years	Prader I, premature pubarche, accelerated growth	13/>154	p.Leu12Met+p.Gln318/p.Val281Leu	NC	Brazil	Present study
2	F	Adult	Asymptomatic	6/31	p.Ser101Asn/p.Val281Leu	—	Brazil	Present study
3	F	Adult	Menstrual irregularities and hirsutism	NA	p.Ser113Phe/p.Val281Leu	NC	Brazil	Present study
4	F	At birth	Positive neonatal screening, 17OHP 106 nM	5/21; Cortisol 360/1118	p.Ser202Gly/p.Gln318	—	Sweden	Present study
5	F	1 month	Prader I, screening value 17OHP 23 nM	NA	p.Ser202Gly/WT	Healthy; carrier	Brazil	Present study
6	M	9 years	Premature pubarche, advanced BA (12.1 y at 9.5 y)	4/11	p.Ser202Gly/WT	Healthy; carrier	Brazil	Present study
7	F	At birth	Prader IV, Na (129 mM)	73/NA	p.(Gln389_Ala391del)/30-kb deletion	SW	Brazil	Present study
8	F	1 month	Prader V. Adrenal crisis day 33: Na (117 mM), K (8.3 mM), hypoglycemia (2.3 mM)	247/NA	p.Thr450Pro/p.Thr450Pro	SW	Iran	[19]
9	M	5 years	Suspicion of penile growth/pseudoprecocious puberty	1.5/NA	p.Arg16Cys/WT	Healthy; carrier	Brazil	Present study
10	F	4 years	Premature pubarche, BA 8.10 yrs at 6.5 yrs of age	2/7	p.Pro267Leu/WT	Healthy; carrier	Brazil	Present study
11	F	Adult	Acne	1.3/9	p.Thr450Met/WT	Healthy; carrier	Brazil	Present study

Reference value/cut-off level 17-OHP: 6 and 30 nM, basal and 60 min, 250 µg Synacthen stimulation test.
Neonatal reference value/cut-off level 100 nM.
Haider et al. 2013 [18], mutation is reported but no patient phenotype description.
NA: not available; SW: salt wasting; NC: nonclassic; BA: bone age; WT: wild type.