Central Hypogonadotropic Hypogonadism: Genetic Complexity of a Complex Disease
Table 1
Human genes involved in CHH.
Genes
Location
Gene ID
Structure (coding exons)
Inheritance
OMIM
Phenotype
KAL1
Xp22.3
3730
14
XR
308700
KS
FGFR1 (KAL2)
8p12
2260
17
AD
147950
KS
FGF8 (KAL6)
10q24
2253
6
AD
612702
nHH
PROK2 (KAL4)
3p13
60675
4
AR
610628
KS
PROKR2 (KAL3)
20p12.3
128674
2
AD, AR
147950
KS, nHH
CHD7 (KAL5)
8q12.2
55636
37
AD
612370
CHARGE, KS, nHH
NELF
9q34.3
26012
14
Digenic
614838
KS
GNRH1
8p21-p11.2
2796
3
AR
614841
nHH
GNRHR
4q21.2
2798
3
AR
146110
nHH
LEP
7q31.3
3952
2
AR
614962
nHH
LEPR
1p31
3953
18
AR
614963
nHH
TAC3
12q13-q21
6866
5
AR
614839
nHH
TACR3
4q25
6870
5
AR
614840
nHH
KISS1
1q32
3814
2
AR
614842
nHH
KISS1R (GPR54)
19p13.3
84634
5
AR
614837
nHH
PCSK1
5q15-q21
5122
14
AR
162150
nHH
WDR11
10q26
55717
29
AD
614858
KS, nHH
HS6ST1
2q21
9394
2
Unclear
614880
KS, nHH
SEMA3A
7p12.1
10371
17
AD, di/oligogenic
614897
KS
SEMA7A
15q22.3-q23
8482
14
Di/oligogenic
607961
nHH, KS
LHB
19q13.32
3972
3
AR
152780
nHH
FSHB
11p13
2488
2
AR
136530
nHH
NDN
15q11.2-q12
4692
1
Unknown
602117
KS, Prader-Willi
TSHZ1 (candidate)
18q22.3
10194
1
AD
614427
Expected: OFC, CAA, hyposmia, probably KS
Gene ID: identification number assigned to a specific gene in NCBI database; OMIM: online catalogue of human genes and genetic disorders, numbers refer to the first search result including the gene name and the term “hypogonadism;” KS: Kallmann syndrome; nHH: normosmic hypogonadotropic hypogonadism; XR: X-linked recessive; AR: autosomic recessive; AD: autosomic dominant; OFC: syndromic orofacial cleft; CAA: congenital aural atresia.
