SHOX Deficiency Phenotypes

Martin Roubicek, Maria Cristina Arriazu and Gabriel Isaac

Endocrinology and Genetics, Hospital Privado de Comunidad 7600 Mar del Plata, Argentina

Address correspondence to: Dr. Martin Roubicek, M.D., Servicio de Endocrinologia, Hospital Privado de Comunidad, Córdoba 4545, 7600 Mar del Plata, Argentina. E-mail: roubicek{at}mdp.edu.ar.

To the editor:

We enjoyed reading the very interesting report by Judith L. Ross and colleagues on SHOX deficiency phenotypes in the December 2001 issue of JCEM (1) and the accompanying editorial by Ron G. Rosenfeld (2). We wish to share with you and your readers some caveats referring to both reports.

1. In the third paragraph of the editorial, Leri-Weill dyschondrosteosis is described as "an autosomal dominant form of mesomelic dysplasia... . "

If, in fact, the SHOX gene, whose abnormalities have been shown to be causally related to the dysplasia, has been located in the pseudoautosomal region of the sex chromosomes (as mentioned in the second paragraph of the editorial), then the correct term for the type of hereditary transmission should be a "pseudoautosomal dominant," a "sex chromosomal dominant," or a "gonosomal dominant" form of mesomelic dysplasia, and the genetics literature should be corrected accordingly. The On-line Mendelian Inheritance in Man entry for Leri-Weill dyschondrosteosis (http://www.ncbi.nlm.nih.gov/Omim/ entry 127300), although still listed among dominant mutations, makes the distinction clear in its first paragraphs.

2. In the last paragraph of the same editorial, on page 5673, it is stated that "Part of the female to male preponderance can be explained ... by the fact that females can obtain an abnormal SHOX gene from either their mother or father, whereas males can only receive an abnormal SHOX gene from their mothers." This statement would be correct for an X-linked dominant condition, such as familial hypophosphatemic rickets. But when the causal abnormal gene is located in the pseudoautosomal region, it can also be found on the Y chromosomal pseudoautosomal region, and thus be transmitted from father to son. This is beautifully illustrated by family 10 in the study by J. L. Ross et al. (1). As may be seen in Ross et al.’s Table 1 (page 5676), in that family the deletion was present in the male proband on his X chromosome, in his mother and sister (obviously) on their X, but in his son on the Y chromosome, implying that a crossover had occurred between the X and Y chromosomes in the proband’s spermatogenesis. Incidentally, this occurrence was not emphasized in the article in question, although it is a beautiful example of a genetic disease previously thought to be autosomal dominant, being in fact a pseudoautosomal or sex chromosomal dominant, with a potentially more severe phenotypic expression in the hemizygote males than in the heterozygote females. This type of inheritance would not explain the female preponderance of affected persons, thus favoring some of the other possible explanations mentioned by Dr. Rosenfeld.

Received February 22, 2003.

References

  1. Ross JL, Scott Jr C, Marttila P, Kowal K, Nass A, Papenhausen P, Abboudi J, Osterman L, Kushner H, Carter P, Ezaki M, Elder F, Wei F, Chen H, Zinn AR 2001 Phenotypes associated with SHOX deficiency. J Clin Endocrinol Metab 86:5674–5680[Abstract/Free Full Text]
  2. Rosenfeld RG 2001 A SHOX to the system. J Clin Endocrinol Metab 86:5672–5673[Free Full Text]




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