A novel interstitial deletion of KAL1 in a Japanese family with Kallmann syndrome

Abstract

We identified a novel interstitial deletion that spanned from exons 5 to 10 of KAL1 in two Japanese brothers with X-linked Kallmann syndrome (KS; MIM no. 308700). Both brothers had hypogonadism, unilateral renal agenesis, and disturbance of the sense of smell, but they had no other neurological manifestations, including mental disturbance. Their mother was confirmed to be an asymptomatic carrier, by use of a comparative multiplex polymerase chain reaction (PCR) analysis. The present patients are further examples of patients with KS without mental disturbance caused by a mutation confined to KAL1.

Similar interstitial deletions of the KAL-1 gene in two Brazilian families with X-linked Kallmann Syndrome

“…Thus, at least two different molecular mechanisms may be responsible for the observed intragenic deletion. Together with the similar deletion previously described by Nagata et al (2000), our data suggest that a recurrent mechanism could predispose to this specific large exon-type deletion.…”

“…Several small deletions, point mutations and a few single-exon deletions have been identified in the KAL-1 gene in patients with KS (Hardelin et al, 1992;Parenti et al, 1995;Georgopoulus et al, 1997;Quinton et al, 1996;Söderlund et al, 2002). Large deletions involving more than one exon of KAL-1 have been reported for exons 13-14 (Bick et al (1992), 3 to 5 (Maya-Nunez et al, 1998, 5 to 10 (Nagata et al, 2000), and 3 to 13 (Massin et al, 2003). Although the breakpoints were not determined in most cases, it is possible that intronic regions flanking these deletions contain repeated elements that might promote nonallelic recombination.…”

“…One of these patients had mental retardation and a horseshoe right kidney in association with KS. Nagata et al (2000) described two brothers with X-linked KS due to a deletion of exons 5-10 of the KAL-1 gene, but neither mental retardation nor bimanual synkinesis were reported to be present. In fact, mental retardation is rarely observed in patients with isolated KS, but has been described in patients affected by associations of several diseases linked to Xp22.3, as contiguous gene syndromes (Meindl et al, 1993;Weissortel et al, 1998).…”

“…Comparative duplex PCR for carrier female status determination was performed, following the procedure described by Nagata et al (2000), in subjects II-11 and III-17 (Family 1) and I-2 (Family 2), mothers of affected males. The reactions included primers for exon 20 of the autosomal NPC1 gene as internal standard to quantify the dosage of KAL-1 exon 7 PCR products.…”

Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH)

“…One-third of IHH patients were familial, while the remaining patients were sporadic, and autosomal dominant, autosomal recessive, and X-linked forms of IHH have been reported (Waldstreicher et al 1996). Protein of KAL1, the gene responsible for the X-linked KS (Legouis et al 1991;Nagata et al 2000), exhibits characteristics as a cell adhesion molecule and is involved in both migration of GnRH cells and olfactory neuronal cells. Failure of GnRH-cell migration has been confirmed in a KS fetus (Schwanzel-Fukuda et al 1989;Hardelin 2001), and mutation in KAL1, DAX, and LHRHR account for $20% of patients with hypogonadotropic hypogonadism (Seminara et al 1999;Oliveira et al 2001;Beranova et al 2001).…”