Inherited Chondrodysplasia Punctata Due to a Deletion of the Terminal Short Arm of an X Chromosome

Abstract

We studied two families with an inherited deletion of the short arm of an X chromosome (Xp) in which affected male offspring have epiphyseal stippling in infancy (chondrodysplasia punctata), nasal hypoplasia, ichthyosis, and mental retardation. The presence of ichthyosis and the apparent pattern of X-linked recessive inheritance prompted investigation of the short arm of the X chromosome through studies of genetic markers and focused cytogenetic analysis. Biochemical studies suggested that there was a deletion of three genes previously mapped to the X-chromosome short arm, including the steroid sulfatase locus, the Xg locus, and the M1C2X locus. Prometaphase chromosomes demonstrated a deletion of Xp at p22.32 in the affected boys, in their obligate-carrier mothers, and in 11 of 25 women at risk as potential carriers. The women carrying the Xp deletion had normal gonadal function and fertility but were shorter than the noncarriers in their families (P less than 0.00001). These findings have implications for the genetic organization of this portion of the human X chromosome and demonstrate that small cytogenetic abnormalities may account for disorders with apparent mendelian patterns of inheritance.

The sex-determining region of the human Y chromosome encodes a finger protein

“…When hybridized to Taql digests, pDP1171 detects fragments of 4.4, 8, and 10 kb, all of which are present in normal males but absent in normal females ( Probe pDP1039. which detects a 5.5-kb Taql fragment on the human X chromosome, was hybridized to Taql-digested DNAs from XYYYY male Oxen, XXXX female GM1416, a normal human male, a normal human female, mouse, hamster, t60-12 (somatic cell hybrid retaining human X chromosome; H. Willard, personal communication), A2-4 (somaticcell hybrid retaining a human X;21 translocation product carrying Xqter-p21; Worton et al, 1984), Cl-T3 (somatic cell hybrid retaining a human X;21 translocation product carrying Xpter-p21; the reciprocal of A2-4), 85-13/8 (somatic cell hybrid retaining a terminally deleted human X, Xqter-p22.3; Curry et al, 1984), 97-115 (somatic cell hybrid retaining a human X-Y translocation product, Xqter-p22.3::Ypll-qter; Bernstein et al. 1978;Bernstein, 1985;Geller et al, 1986), and HY.22AZAl (somatic cell hybrid retaining a dicentric X chromosome, Xqter-p22.3::Xp22.1-qter; Ferraro et al, 1980;M.…”

Long-range restriction map of the terminal part of the short arm of the human X chromosome.

“…While loci for short stature (SS), X-linked recessive chondrodysplasia punctata (CDPX; McKusick no. 21510), and mental retardation (MR) are all localized distal to the X-linked ichtyosis (XLI) locus (13)(14)(15)(16) (STS locus), Kallmann syndrome (KAL) locus maps proximal to STS (17).…”

Isolation and characterization of a steroid sulfatase cDNA clone: genomic deletions in patients with X-chromosome-linked ichthyosis.

“…2, lanes 2 and 3). One hybrid expresses human levels of STS activity but lacks MXYS1 (MIC2), which has been assigned to Xp22.3, and the other lacks both STS activity and the MXYS1 locus (26). The observation of a positive signal in the former hybrid (lane 2) and not the latter (lane 3) provides a clear localization of the sequences recognized by p422 to Xp22.3.…”