Table 2.

Phenotypic and Genotypic Characteristics of Women With IHH Treated With iv GnRH

Subject no.	Age, y	BMI, kg/m2	Baseline Study	Partial Puberty	Olfactory Phenotype	Nonreproductive Phenotype	Gonadotropin Levels (d 1–7)a		Genetics
							FSH	LH	Gene	Variant	Functional Data (Reference)	Prediction Programsb
Normal response
1	20.0	22.7	A	N	nIHH	High arched palate, scoliosis			TACR3	p.W208X	Nonsense
2	22.8	21.3	A	N	nIHH				Neg
3	36.9	23.5	P	Y	nIHH	Cleft lip and palate, widely-spaced teeth			Neg
4	28.9	20.0	A	N	nIHH	Partial empty sella			N.A.
5	36.4	28.3	P	Y	nIHH	Marfanoid habitus			Neg
6	17.6	18.0	A	N	KS	Ocular defect			CHD7	c.3202–5 T>C (splice)		0c
7	26.6	33.6	A	Y	KS	Ocular defect, short fourth metacarpal			FGFR1	p.L630P		4
8	33.2	18.0	A	N	KS				Neg
9	38.6	25.4	P	Y	KS	Hearing loss			KAL1	p.K185N		2
10	31.5	18.8	A	N	KS				Neg
11	23.0	21.7	P	N	KS				N.A.
12	16.8	21.5	P	N	KS				Neg
13	18.5	18.9	A	N	KS	Clinodactyly			Neg
14	31.8	25.9	P	Y	KS				Neg
15	25.5	24.3	P	Y	nIHH				N.A.
16	41.9	35.6	P	Y	nIHH				Neg
17	28.5	22.1	P	N	nIHH				Neg
18	23.8	25.6	A	N	nIHH				TAC3	p.R80S		4
19	38.6	18.2	A	N	KS	Flat nasal bridge, PDA, hypoplastic fifth finger (CHAR syndrome)			N.A.
20	32.2	26.5	P	Y	KS				Neg
21	34.8	18.1	A	Y	nIHH				N.A.
22	19.9	26.9	A	Y	KS	Widely-spaced teeth			CHD7	p.L373F		1
Abnormal, pituitary resistance
23	23.4	20.9	A	Y	nIHH		↓	↓	Neg
24	27.9	21.7	P	N	KS	Short fourth metacarpal	NI	↓	FGFR1, GNRHR	p.R470L; p.Q106R, p.R262 (all partiald)	(26, 35, 37)
25	39.4	42.8	A	Y	KS	Clinodactyly, flat nasal bridge	↓	↓	Neg
26	30.0	23.3	A	N	nIHH	Partial empty sella	NI	↓	PROKR2	p.L173R (partial)	(25)
27	35.5	28.2	A	Y	nIHH		↓	↓	GNRHR	p.M1T + p.R139H (complete); p.Q106R (partial)	Start codon (35)
28	29.9	43.8	A	Y	nIHH		↓	↓	Neg
29	43.0	36.0	A	Y	nIHH	Widely-spaced teeth	↓	↓	Neg
30	27.1	37.7	A	Y	KS		NI	↓	Neg
31	33.5	27.7	A	Y	nIHH		↓	↓	N.A.
32	17.6	26.4	A	N	KS		↓	↓	Neg
33	32.3	32.4	A	Y	KS	Syndactyly, pes planus	↓	↓	Neg
34	26.7	20.1	P	Y	nIHH		NI	↓	GNRHR	p.N10K+p.Q11K (partial); p.P320L (complete)	(34, 36)
Abnormal, ovarian resistance
35	41.0	22.3	A	N	nIHH		↑	↑	Neg
36	35.9	22.8	A	N	nIHH	Mitral valve prolapse	↑	↑	Neg
37	31.2	28.9	A	N	nIHH	Cleft palate	↑	NI	Neg
63-year-old woman
38	63.0	23.5	A	N	nIHH		↑	↑	PROK2	p.155fsX1 (complete)	(32)

Abbreviations: A, apulsatile; KS, Kallmann's (anosmic or hyposmic IHH); N, no; N.A., DNA sample not available; Neg, negative; NI, normal; nIHH, normosmic IHH; P, pulsatile; Y, yes; ↑, high; ↓, low.

^aGonadotropin levels during the first week of GnRH treatment relative to normal IHH responders.

^bNumber of prediction programs (of 5) predicting this mutation to be deleterious.

^cA single prediction program, Human Splicing Finder, does not predict that this variant will alter splicing.

^dRefers to partial or complete loss of function.