Study on KAL1 Gene Mutations in Idiopathic Hypogonadotropic Hypogonadism Patients with X-Linked Recessive Inheritance

Document Type : Original Article

Authors
Atefeh Ahmadzadeh 1
Elahe Ghods 1
Majid Mojarrad 2
Robab Aboutorabi 3
Mojgan Afkhamizadeh 3
Shokoofeh Bonakdaran 3
Zohreh Mosavi 3
Seyed Morteza Taghavi 3
Mohammad Hassanzadeh Nazarabadi 2
1 Department of Medical Genetics, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran
2 Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3 Department of Endocrinology Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract
Idiopathic hypogonadotropic hypogonadism (IHH) is a condition caused by low doses of hypothalamic
gonadotropin-releasing hormone (GnRH) leading to absence or incomplete sexual maturation. One of the
disorders leading to IHH is Kallmann syndrome which is characterized by GnRH deficiency with anosmia or
hyposmia. This disorder generally occurs as a hereditary syndrome with X-linked recessive inheritance pattern.
However, autosomal dominant or recessive and sporadic cases have also been reported. KAL1 is the most
common mutated gene among these patients. The aim of this study was to determine the mutation spectrum of
KAL1 gene in twenty patients. KAL1 exons were amplified by PCR method and the products were assessed by
high resolution melting (HRM) technique. In addition, for one of the patients, all coding exons of the KAL1 gene
were sequenced. Deletion of exons 4, 5 and 6 were evident in 5%, 10%, and 10% of patients, respectively.
Furthermore, HRM results showed hemizygous mutation of exon 12 with more than 95% probability in 25% of
patients. Finding these mutations could be helpful in the early diagnosis and presymptomic treatment of Kallman
syndrome.
Keywords
Idiopathic hypogonadotropic hypogonadism
kallmann syndrome
KAL1 gene
X-linked recessive
GnRH