A patient with an interstitial deletion in Xp22.3 locates the gene for X-linked recessive chondrodysplasia punctata to within a one megabase interval

Abstract

A male patient carrying an interstitial deletion in Xp22.3 and affected by Kallmann syndrome, X-linked ichthyosis and mental retardation, but without chondrodysplasia punctata or short stature, was investigated with molecular probes from the distal Xp22.3 region. By means of a novel probe, M115, from the relevant region, the distal deletion breakpoint was shown to be between 3.18 and 3.57 Mb from Xptel. As the patient is not affected by X-linked recessive chondrodysplasia punctata, the gene for this disease can therefore be located to within an interval of less than one megabase proximal to the pseudoautosomal boundary. If the chondrodysplasia punctata gene is associated with a CpG island, this leaves only two islands at 2760 and 3180 kb from the Xp telomere as the most promising candidate sites for this gene.

L�ri-Weill syndrome as part of a contiguous gene syndrome at Xp22.3

“…The boy's clinical picture closely resembles that observed in patients with chromosome aberrations and contiguous gene syndromes involving Xp22.3 [Agematsu et al, 1988;Ballabio et al, 1987Ballabio et al, , 1989Curry et al, 1984;Klink et al, 1994;Meindl et al, 1993;Nishimura et al, 1991;Petit et al, 1990;Schnur et al, 1989]. He has a peculiar nasal shape with short columella and groove between the alae and the nasal tip.…”

“…Short stature is due to hetero-or nullisomy for the SHOX-gene [Rao et al, 1997]. Bilateral Madelung deformity is the key clinical sign in the Léri-Weill syndrome [Langer, 1965] (S. Spranger et al, submitted for publication) and has occasionally been mentioned in patients with rearrangements and deletions of Xp22.3 [Guichet et al, 1997;Eswara et al, 1992;Castillo et al, 1985;Meindl et al, 1993;Klink et al, 1994;Pfeiffer et al, 1980;Seidel et al, 1997]. Recently, two groups found either deletions (by FISH analysis) or point mutations in the SHOX Fig 4. a: X-and Y-chromosomes of the son after two-color hybridization of microdissection probe for the short arm of the X-chromosomes (digoxigenin-Cy3, red) together with YAC clone yWXD2539 (biotin-FITC, green) from the distal part of the pseudoautosomal region Xp22.3.…”

“…Depending on the breakpoint, interstitial and terminal deletions of Xp22.3 in males are associated with monogenic disorders, such as short stature, chondrodysplasia punctata, mental retardation, X-linked ichthyosis and/or Kallmann syndrome [Agematsu et al, 1988;Ballabio et al, 1987Ballabio et al, , 1989Bick et al, 1989;Curry et al, 1984;Klink et al, 1994;Meindl et al, 1993;Nishimura et al, 1991;Petit et al, 1990;Schnur et al, 1989]. Females need only one active copy of this region to be normal with the exception of the genes located in the pseudoautosomal region (PAR), such as the SHOX gene [Rao et al, 1997].…”

Steroid sulfatase deficiency and contiguous gene deletion syndrome amongst pregnant patients with low serum unconjugated estriols

“…In a very recent publication, Kent et al (2008) described an association between STS deficiency and attention deficit hyperactivity disorder (ADHD). Sporadic cases of STS deficiency with additional features due to a deletion of contiguous genes have also been reported (Ballabio et al, 1989;Bick et al 1989;Klink et al,1994;Muroya et al, 1996;Weissörtel R et al, *Correspondence to: Sylvie Langlois, Medical Genetics, University of British Columbia, C234, 4500 Oak Street, Vancouver, BC, Canada V6H 3N1. E-mail: slanglois@cw.bc.ca † Presented at the 14th Meeting of the International Society of Prenatal Diagnosis, Vancouver, June 1-4, 2008. 1998; Gohlke et al, 2000).…”

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

“…2c). (Table 1) (Bick et al 1992;Hardelin et al 1992;Meindl et al 1993;Hardelin et al 1993a,b;Klink et al 1994;Martul et al 1995;Parenti et al 1995;Quinton et al 1996;Georgopoulos et al 1997;Gu et al 1998;O'Neill et al 1998;Weissörtel et al 1998;MayaNúñez et al 1998a,b andIzumi et al 1999). Both of the patients described here had hypogonadism and hyposmia (the two hallmarks of KS), but they had no other neurological symptoms.…”