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. 2015 Dec 3:7:64-9.
doi: 10.1016/j.mgene.2015.12.001. eCollection 2016 Feb.

Clinical characteristics and follow-up of 5 young Chinese males with gonadotropin-releasing hormone deficiency caused by mutations in the KAL1 gene

Juan Li  1 , Niu Li  2 , Yu Ding  1 , Xiaodong Huang  1 , Yongnian Shen  1 , Jian Wang  3 , Xiumin Wang  1
Affiliations

Clinical characteristics and follow-up of 5 young Chinese males with gonadotropin-releasing hormone deficiency caused by mutations in the KAL1 gene

Juan Li et al. Meta Gene. .

Abstract

Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) pertains to a group of genetic disorders consisting of anosmic hypogonadotropic hypogonadism (Kallmann syndrome, KS) and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). KS is genetically heterogeneous. We hereby present 5 young male patients with GnRH deficiency caused by mutations in the KAL1 gene. Their ages ranged from 9 months to 16 years. They were referred to our department for an endocrine consultation for micropenis. Hormone assays showed low circulating gonadotropins and testosterone. Molecular studies revealed KAL1 mutations in all cases, three reported nonsense sequence variants in the KAL1 gene were detected in 4 patients, respectively (c.784C > T (p.Arg 262*), c.1267C > T (p.Arg423*), and c.1270C > T (p.Arg424*)), and one patient harbored a novel hemizygous sequence variant [c.227G > A (p.Trp76*)]. Only one patient presented short stature without growth hormone deficiency and anosmia. Another patient had bilateral eyelid ptosis, trichiasis, and refractive error. This is the first report on the co-occurrence of a KAL1 gene mutation and tent-like upper lip in four patients. All of our cases had normal olfactory bulbs and showed no renal agenesis, cleft lip/palate, and hearing impairment. These cases expand our knowledge of the phenotype associated with KAL1 sequence variations, although the precise mechanism by which KAL1 gene influences the development of this phenotype is still unknown.

Keywords: Clinical phenotype; Isolated gonadotropin-releasing hormone deficiency; KAL1 mutations; Kallmann syndrome.

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Figures

Fig. 1
Fig. 1
Penis and testis abnormalities. A–D. Cases 2–5have micropenis. Small testis, and thicker upper lip. The parents of Case 1 refused to provide photos of their child.
Fig. 2
Fig. 2
A novel mutation was identified in the KAL1 gene of Case 2. Sequences show a hemizygous nonsense mutation, c.227G > A (p.Trp76*) in exon 2 of the KAL1 gene of the patient, whereas his mother was heterozygous for the same mutation.
See this image and copyright information in PMC

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