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Background: Calcium kidney stones are common and recurrences are often not preventable by available empiric remedies. Their etiology is multifactorial and polygenic, and an increasing number of genes are implicated. Their identification will enable improved management. Methods: DNA from three stone‐formers in a Southampton family (UK) and two from an Italian family were analyzed independently by whole exome sequencing and selected variants were genotyped across all available members of both pedigrees. A disease variant of SLC25A25 (OMIM 608745), encoding the mitochondrial ATP‐Mg/Pi carrier 3 (APC3) was identified, and analyzed structurally and functionally with respect to its calcium‐regulated transport activity. Results: All five patients had a heterozygous dominant SLC25A25 variant (rs140777921; GRCh37.p13: chr 9 130868670 G>C; p.Gln349His; Reference Sequence NM_001006641.3). Non‐stone formers also carried the variant indicating incomplete penetrance. Modeling suggests that the variant lacks a conserved polar interaction, which may cause structural instability. Calcium‐regulated ATP transport was reduced to ~20% of the wild type, showing a large reduction in function. Conclusion: The transporter is important in regulating mitochondrial ATP production. This rare variant may increase urine lithogenicity through impaired provision of ATP for solute transport processes in the kidney, and/or for purinergic signaling. Variants found in other genes may compound this abnormality. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "The association of 330 interleukin-2 gene polymorphism and hla-dr15 allele in iranian patients with multiple sclerosis" by A. Sayad.

A letter to the editor is presented in response to the article "Anti-EBNA-1 IgG is not a reliable marker of multiple sclerosis clinical disease activity," by G. Ingram and colleagues in the 2010 issue.