A novel mutation of the KAL1 gene in monozygotic twins with Kallmann syndrome.
OBJECTIVE
Kallmann syndrome is defined by the association of hypogonadotropic hypogonadism and anosmia. The KAL1 gene is responsible for the X-linked form of Kallmann syndrome. In this study we describe monozygotic twins with Kallmann syndrome due to the same mutation in the KAL1 gene.


METHODS
We studied male monozygotic twins with Kallmann syndrome.


METHODS
We analyzed the KAL1 gene using the PCR-direct sequencing method. The twins' mother was examined for the identified mutation.


RESULTS
We identified a 14 bp deletion from codon 419 in exon 9 (Pro419del14) in both KAL1 genes of the twins. This was a novel mutation in the KAL1 gene and was responsible for Kallmann syndrome. As Pro419del14 was not detected in the mother of the twins, Pro419del14 was a germline mutation originating from them. These monozygotic twins showed different LH and FSH responses to LH-RH stimulation and different phenotypes such as complications, physiques and psychiatric characters.


CONCLUSIONS
We report an identical KAL1 gene mutation in the monozygotic twins with Kallmann syndrome. As these monozygotic twins showed different phenotypes in some respects, we suggest that factors other than mutations in the KAL1gene affect the symptomatic features of Kallmann syndrome.
Matsuo
T
T
Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
Okamoto
S
S
Izumi
Y
Y
Hosokawa
A
A
Takegawa
T
T
Fukui
H
H
Tun
Z
Z
Honda
K
K
Matoba
R
R
Tatsumi
K
K
Amino
N
N
D000328:Adult; D001483:Base Sequence; D001827:Body Height; D001835:Body Weight; D015815:Cell Adhesion Molecules / Q000235:genetics*; D004200:Diseases in Twins / Q000235:genetics*; D005091:Exons; D016326:Extracellular Matrix Proteins; D005260:Female; D018392:Genomic Imprinting; D018095:Germ-Line Mutation; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D017436:Kallmann Syndrome / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009419:Nerve Tissue Proteins; D010375:Pedigree; D010907:Pituitary Hormones / Q000097:blood; D016133:Polymerase Chain Reaction; D011392:Proline; D012016:Reference Values; D017384:Sequence Deletion; D014430:Twins, Monozygotic
C076266:ANOS1 protein, human; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D012739:Gonadal Steroid Hormones; D009419:Nerve Tissue Proteins; D010907:Pituitary Hormones; D011392:Proline