Point mutation associated with X-linked dominant Charcot-Marie-Tooth disease impairs the P2 promoter activity of human connexin-32 gene

Allelic variants in the 5` non-coding region of the connexin32 gene: possible pitfalls in the diagnosis of X linked Charcot-Marie-Tooth neuropathy (CMTX)

“…11 In contrast, we found the same −713A allele in about 50% of chromosomes of CMT patients and in an equal proportion of chromosomes derived from healthy volunteers. Our data imply that the −713A allele represents a harmless polymorphism that neither acts as a significant risk factor for developing peripheral neuropathy nor modifies the course of the disease in the white German population.…”

“…9 10 Here we report two additional alleles within this region initially assumed to be of phenotypic relevance. One of these (G−713A) has been recently reported as a disease causing mutation, 11 whereas in our series it has been identified as a harmless polymorphism. 12 …”

“…The −713A allele is common in the German population but was not found in the chromosomes of over 100 Taiwanese controls. 11 However, these findings are not necessarily contradictory since some single nucleotide polymorphisms (SNP) are specific to particular ethnic groups while others can be found with similar allele frequencies throughout the world. 29 30 The sequence variation creates a unique NcoI restriction site allowing a convenient genetic test using PCR amplified DNA.…”

Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease

“…This problem is in large part due to the fact that there are no simple ways to discern regulatory elements from nonfunctional sequences or to ascertain whether mutant phenotypes are caused by regulatory mutations. Among Mendelian disorders associated with noncoding mutations, only a few cases are described that clearly link alterations in distant cis-acting regulatory regions to the cause of the disease (Ionasescu et al 1996;Wang et al 2000;Enattah et al 2002;Lettice et al 2003;Tsui et al 2003), and these documented cases predominantly correspond to large chromosomal aberrations (Curtin et al 1985;Curtin and Kan 1988;Cimbora et al 2000;Kleinjan et al 2001;Chuzhanova et al 2003). Structural variation in the human genome described as large-scale polymorphisms has been recently shown to be more common than previously anticipated (Sebat et al 2004); therefore, the extent to which large noncoding duplications and deletions have an impact on human biology remains a largely unanswered question.…”

A novel hearing loss-related mutation occurring in the GJB2 basal promoter

“…The remaining cases possibly have pathogenic mutations yet to be found in the promoter region or other non-coding regions of GJB2 . Notably, pathogenic mutations have been identified in the 5′ untranslated region (UTR) and promoter region of GJB1 (Cx32),6 – 8 another gene of the connexin family. In this paper, we report the genetic identification and functional analysis of the first GJB2 promoter mutation.…”