'Silent' carriage of two familial Mediterranean fever gene mutations in large families with only a single identified patient

• Published in: Clinical genetics Vol. 82; no. 3; pp. 288 - 291
• Main Authors: Camus, D, Shinar, Y, Aamar, S, Langevitz, P, Ben-Zvi, I, Livneh, A, Lidar, M
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2012; Wiley-Blackwell
• Subjects: Amyloidosis; Biological and medical sciences; Colchicine; Diseases of the osteoarticular system; Familial Mediterranean fever; Familial Mediterranean Fever - genetics; FMF; Fundamental and applied biological sciences. Psychology; Genes; Genetic disorders; Genetic screening; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Genotype & phenotype; Genotypes; Humans; Inflammatory joint diseases; Medical genetics; Medical sciences; Molecular and cellular biology; Mutation; Phenotype; phenotype III; Point mutation; Prophylaxis; Pyrin protein; Risk factors; Siblings; silent carriage; Transformation; Human; Family study; Diseases of the osteoarticular system; Patient; Asymptomatic; Genetic disease; Inflammatory disease; silent carriage; Phenotype; Gene; Familial mediterranean fever; Genetics; phenotype III; Mutation; Colonization; FMF
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2011.01785.x

Camus D, Shinar Y, Aamar S, Langevitz P, Ben‐Zvi I, Livneh A, Lidar M. ‘Silent’ carriage of two familial Mediterranean fever gene mutations in large families with only a single identified patient.
The presence of two mutations in the familial Mediterranean fever gene, without overt familial Mediterranean fever (FMF), designated as phenotype III, predisposes to developing ‘silent’ AA amyloidosis, recognized as phenotype II, due to the absence of medical supervision and colchicine prophylaxis. We sought to determine the prevalence of phenotype III in large families with only one subject affected with FMF, in order to assess the population at risk for transformation to phenotype II. A total of seven large families were recruited for the study. Siblings were screened for MEFV mutations and underwent a clinical interview to assess for unrecognized FMF manifestations. Phenotype III, most commonly associated with a V726A/E148Q genotype, was detected in 10% of siblings of index cases from informative families, corresponding to a 10‐fold increase in comparison to the expected rate in the general population (p < 0.01). Unnoticed ‘FMF‐like’ manifestations were detected among two siblings in the five families in which the index case was heterozygous, but in none of the siblings of the homozygous index cases. The enrichment for phenotype III and detection of occult FMF in large families, in which only a single member is afflicted with FMF, mandates routine clinical evaluation and genetic screening of siblings.