[en] Heterozygote deletions or mutations of pseudoautosomal 1 region (PAR1) encompassing the short stature homeobox-containing (SHOX) gene cause Leri-Weill Dyschondrosteosis (LWD), which is a dominantly inherited osteochondroplasia characterized by short stature with mesomelic shortening of the upper and lower limbs and Madelung deformity of the wrists. SHOX is expressed by both sex chromosomes in males and females and plays an important role in bone growth and development. Clinically, the LWD expression is variable and more severe in females than males due to sex differences in oestrogen levels. Here, we report two familial cases of LWD with a large Xp terminal deletion (approximately 943 kb) of distal PAR1 encompassing the SHOX gene. In addition, the proband had mental retardation which appeared to be from recessive inheritance in the family.
BELIN V., CUSIN V., VIOT G., GIRLICH D., TOUTAIN A., MONCLA A., VEKEMANS M, LE MERRER M., MUNNICH A., CORMIER-DAIRE V.: SHOX mutations in dyschondrosteosis (Leri-Weill syndrome). Nat. Genet., 1998, 19(1), 67-69.
BENITO-SANZ S., DEL BLANCO D.G., AZACARMONA M, MAGANO L.F., LAPUNZINA P., ARGENTE J., CAMPOS-BARROS A., HEATH K.E.: PAR1 deletions downstream of SHOX are the most frequent defect in a Spanish cohort of Leri-Weill dyschondrosteosis (LWD) probands. Hum. Mutat., 2006, 27(10), 1062.
BENITO-SANZ S. THOMAS N.S., HUBER C., GORBENKO DEL BLANCO D., AZA-CARMONA M., CROLLA J.A., MALONEY V., RAPPOLD G., ARGENTE J., CAMPOS-BARROS A., CORMIER-DAIRE V., HEATH K.E.: A novel class of Pseudoautosomal region 1 deletions downstream of SHOX is associated with Leri-Weill dyschondrosteosis. Am. J. Hum. Genet., 2005, 77(4), 533-544.
CLEMENT-JONES M., SCHILLER S., RAO E., BLASCHKE R.J., ZUNIGA A., ZELLER R., ROBSON S. C., BINDER G., GLASS I., STRACHAN T., LINDSAY S., RAPPOLD G.A.: The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum. Mol. Genet., 2000, 9(5), 695-702.
D'ESPOSITO M., CICCODICOLA A., GIANFRANCESCO F, ESPOSITO T., FLAGIELLO L., MAZZARELLA R., SCHLESSINGER D., D'URSO M.: A synaptobrevin-like gene in the Xq28 pseudoautosomal region undergoes X inactivation. Nat. Genet., 1996, 13(2), 227-229.
FUKAMI M., KATO F., TAJIMA T., YOKOYA S., OGATA T.: Transactivation function of an approximately 800-bp evolutionarily conserved sequence at the SHOX 3′ region: implication for the downstream enhancer. Am. J. Hum. Genet., 2006, 78(1), 167-170.
FUKAMI M., NISHI Y., HASEGAWA Y., MIYOSHI Y., OKABE T., HAGA N., NAGAI T., TANAKA T., OGATA T.: Statural growth in 31 Japanese patients with SHOX haploinsufficiency: support for a disadvantageous effect of gonadal estrogens. Endocr. J., 2004, 51(2), 197-200.
GEDEON A.K., DONNELLY A.J., MULLEY J.C., KERR B., TURNER G.: How many X-linked genes for non-specific mental retardation (MRX) are there? Am. J. Med. Genet., 1996, 64(1), 158-162.
KOSHO T., MUROYA K., NAGAI T., FUJIMOTO M., YOKOYA S., SAKAMOTO H., HIRANO T., TERASAKI H., OHASHI H., NISHIMURA G., SATO S., MATSUO N., OGATA T.: Skeletal features and growth patterns in 14 patients with haploinsufficiency of SHOX: implications for the development of Turner syndrome. J. Clin. Endocrinol. Metab., 1999, 84(12), 4613-4621.
RIED K., MERTZ A., NAGARAJA R., TRUSGNICH M., RILEY J.H., ANAND R., LEHRACH H., PAGE D., ELLISON J.W., RAPPOLD G.: Characterization of a YAC contig spanning the pseudoautosomal region. Genomics, 1995, 29(3), 787-792.
ROBERTSON S.P., SHEARS D.J, OEI P., WINTER R.M., SCAMBLER P.J., AFTIMOS S., SAVARIRAYAN R.: Homozygous deletion of SHOX in a mentally retarded mate with Langer mesomelic dysplasia. J. Med. Genet., 2000, 37(12), 959-964.
SCHILLER S., STRANGER S., SCHECHINGER B., FUKAMI M., MERKER S., DROP S.L., TROGER J., KNOBLAUCH H., KUNZE J., SEIDEL J., RAPPOLD G.A.: Phenotypic variation and genetic heterogeneity in Leri-Weill syndrome. Eur. J. Hum. Genet., 2000, 8(1), 54-62.
SHEARS D.J., VASSAL H.J., GOODMAN F.R., PALMER R.W., REARDON W., SUPERTI-FURGA A., SCAMBLER P.J., WINTER R.M. Mutation, deletion of the pseudoautosomal. gene SHOX cause Leri-Weill dyschondrosteosis. Nat. Genet., 1998, 19(1), 70-73.
SPRANGER S., SCHILLER S., JAUCH A., WOLFF K., RAUTERBERG-RULAND I., HAGER D., TARIVERDIAN G., TROGER J., RAPPOLD G.: Leri-Weill syndrome as part of a contiguous gene syndrome at Xp22.3. Am. J. Med. Genet., 1999, 83(5), 367-371.