A Novel GJC2 Mutation Associated with Hypomyelination and Müllerian Agenesis Syndrome: Coincidence or a New Entity?

Abstract

In recent years, several new white matter diseases have been identified based on magnetic resonance imaging and clinical findings. For most newly defined disorders the genetic basis has been identified. However, there is still a large group of patients without a specific diagnosis. Hypomyelinating leukodystrophies are the largest group among them. In some disorders characterized by hypomyelination only central nervous system involvement is observed, but in some disorders involvement of other organs is observed as well, such as eyes or teeth. Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating disorder of the central nervous system characterized by nystagmus, ataxia, and progressive spasticity. The disease is caused by mutations in GJC2, the gene that encodes the gap junction protein connexin 47. Here we describe hypomyelination and Müllerian agenesis syndrome in a girl who is homozygous for a novel mutation in the GJC2 gene. It is an open question whether this is an association by chance or a feature of PMLD not previously noted.

Keywords

hypomyelination - Müllerian agenesis - Pelizaeus-Merzbacher-like disease

• References

• 1 Schiffmann R, van der Knaap MS. The latest on leukodystrophies. Curr Opin Neurol 2004; 17 (2) 187-192
• 2 van der Knaap MS, Breiter SN, Naidu S, Hart AAM, Valk J. Defining and categorizing leukoencephalopathies of unknown origin: MR imaging approach. Radiology 1999; 213 (1) 121-133
• 3 Timmons M, Tsokos M, Asab MA , et al. Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia. Neurology 2006; 67 (11) 2066-2069
• 4 Wolf NI, Harting I, Boltshauser E , et al. Leukoencephalopathy with ataxia, hypodontia, and hypomyelination. Neurology 2005; 64 (8) 1461-1464
• 5 Zara F, Biancheri R, Bruno C , et al. Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination and congenital cataract. Nat Genet 2006; 38 (10) 1111-1113
• 6 van der Knaap MS, Naidu S, Pouwels PJ , et al. New syndrome characterized by hypomyelination with atrophy of the basal ganglia and cerebellum. AJNR Am J Neuroradiol 2002; 23 (9) 1466-1474
• 7 Griffin JE, Edwards C, Madden JD, Harrod MJ, Wilson JD. Congenital absence of the vagina. The Mayer-Rokitansky-Kuster-Hauser syndrome. Ann Intern Med 1976; 85 (2) 224-236
• 8 Orthmann-Murphy JL, Salsano E, Abrams CK , et al. Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. Brain 2009; 132 (Pt 2) 426-438
• 9 Henneke M, Combes P, Diekmann S , et al. GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease. Neurology 2008; 70 (10) 748-754