title: KAL, a gene mutated in Kallmann's syndrome, is expressed in the first trimester of human development.
abstract: Kallmann's syndrome (KS) is characterised by the association of anosmia and isolated hypogonadotrophic hypogonadism (IHH). Mutations of the KAL gene which is located at Xp22.3 cause X-linked KS (XKS). In this study we used the reverse transcriptase polymerase chain reaction and in situ hybridisation to examine the developmental expression of KAL in the first trimester of pregnancy, the earliest stage of human gestation examined thus far. At 45 days after fertilisation KAL mRNA was detected in the spinal cord, the mesonephros and metanephros but not in the brain. Later in gestation, at 11 weeks, the gene was expressed in the developing olfactory bulb, retina and kidney. This expression pattern correlates with the clinical findings in XKS since olfactory bulb dysgenesis with subsequent defective neural migration causes anosmia and IHH. Additionally, renal agenesis occurs in 40% of patients. Therefore this study provides strong evidence that KAL expression is required for the normal development of the olfactory bulb and kidney in the first trimester of human pregnancy.
authors.affiliation: Division of Endocrinology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: V M
authors.initials: VM
authors.lastname: Duke
authors.forename: P J
authors.initials: PJ
authors.lastname: Winyard
authors.forename: P
authors.initials: P
authors.lastname: Thorogood
authors.forename: P
authors.initials: P
authors.lastname: Soothill
authors.forename: P M
authors.initials: PM
authors.lastname: Bouloux
authors.forename: A S
authors.initials: AS
authors.lastname: Woolf
mesh_terms: D001483:Base Sequence; D005260:Female; D005333:Fetus / Q000378:metabolism*; D015870:Gene Expression; D005865:Gestational Age; D006801:Humans; D017403:In Situ Hybridization; D017436:Kallmann Syndrome / Q000235:genetics*; D007668:Kidney / Q000737:chemistry / Q000196:embryology; D008650:Mesonephros / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D009830:Olfactory Bulb / Q000737:chemistry / Q000196:embryology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D013116:Spinal Cord / Q000737:chemistry / Q000196:embryology; D014960:X Chromosome
chemical_list: D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase