� 2007 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 143A:1129 (2007)

Correspondence

Familial Multiple Pterygium Syndrome (MPS)Is Not Associated With CHRNG Gene Mutation

Paolo Prontera,1* Julie Vogt,3 Carole McKeown,3 and Alberto Sensi21University of Perugia, Medical Genetics Unit, Perugia, Italy2University of Ferrara, Medical Genetics Unit, Ferrara, Italy

3Clinical Genetics Unit, Birmingham Women’s Hospital, West Midlands, UK

Received 20 December 2006; Accepted 30 December 2006

How to cite this article: Prontera P, Vogt J, McKeown C, Sensi A. 2007. Familial multiple pterygiumsyndrome (MPS) is not associated with CHRNG gene mutation. Am J Med Genet Part A 143A:1129.

To the Editor:

We recently published an article entitled ‘‘FamilialOccurrence of Multiple Pterygium Syndrome:Expression in a Heterozygote of the Recessive Formor Expressed Variability of the Dominant Form?’’[Prontera et al., 2006], describing a 6-year-old girlwho fits classical Escobar MPS (EMPS) phenotype,and whose father showed minor clinical and radio-logical signs of the syndrome (difficulty in openingthe mouth widely, scoliosis, pectus excavatum,hands with slight cutaneous syndactyly, bilateralsingle palmar creases and malformed carpal bones).

A gene responsible for some cases of lethalMPS (LMPS) and EMPS has now been identified[Hoffmann et al., 2006; Morgan et al., 2006]. Theauthors demonstrated that, in recessive pedigrees,LMPS and EMPS are both caused by mutations in theCHRNG gene (embryonal g-subunit of the acetylcho-line receptor). Mutations were found in 13 out of22 families, suggesting genetic heterogeneity.Wetherefore performed molecular analysis of theCHRNG gene for our proband. Primers weredesigned to amplify the coding exons of CHRNG.PCR products were sequenced from forward andreverse strands on an ABI 3730 DNA analyzer[Morgan et al., 2006]. The analysis failed to detect amutation in CHRNG. Although the molecular screen-ing would not have detected a CHRNG deletion,a missense or frameshift mutation resulting in adominant negative effect was considered the mostlikely mechanism for autosomal dominant MPS.

In conclusion, MPS is a phenotypically andgenetically heterogeneous condition. As autosomaldominantly inherited MPS is rarely recognized,clinical case reports emphasize the need to examinethe parents of affected individuals. The familialfindings of MPS in our family prompted moleculartesting of the CHRNG gene. However, the molecularresults did not clarify the inheritance pattern in thisfamily, and it remains uncertain whether this orother genes may be the cause of autosomal dominantMPS.

REFERENCES

Hoffmann K, Muller S, Strickler S, Megarbane A, Rajab A, LindnerTH, Cohen M, Chouery E, Adaimy L, Ghanem I, Delague V,Boltshauser E, Talim B, Horvath R, Robinson PN, LochmullerH,Hubner C, Mundlos S. 2006. Escobar syndrome is a prenatalmyasthenia causedbydisruption of the acetylcholine receptorfetal g subunit. Am J Hum Genet 79:303–312.

Morgan NV, Brueton LA, Cox P, Greally MT, Tolmie GJ, Pasha S,Aligianis IA, van Bokhoven H, Marton T, Al-Gazali L, MortonJEV, Oley C, Johnson CA, Trembath RC, Brunner HG, MaherER. 2006. Mutations in the embryonal subunit of theacetylcholine receptor (CHRNG) cause lethal and Escobarvariants of multiple pterygium syndrome. Am J Hum Genet79:390–395.

Prontera P, Sensi A, Merlo L, Garani G, Cocchi G, Calzolari E.2006. Familial occurrence of multiple pterygium syndrome:Expression in a heterozygote of the recessive form orexpressed variability of the dominant form? Am J Med GenetPart A 140A:2227–2230.

*Correspondence to: Dr. Paolo Prontera, Genetica Medica, ViaBrunamonti, 51 Perugia 06122, Italy. E-mail: pprontera@hotmail.com

DOI 10.1002/ajmg.a.31698