A family with partially penetrant multicentric carpotarsal osteolysis due to gonadal mosaicism: First reported case

Multicentric carpotarsal osteolysis (MCTO) is an autosomal dominant condition characterized by carpal–tarsal abnormalities; over half of affected individuals also develop renal disease. MCTO is caused by mutations of MAFB; however, there is no clear phenotype–genotype correlation. We describe the fi...

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Bibliographic Details
Published in:American journal of medical genetics. Part A 2021-08, Vol.185 (8), p.2477-2481
Main Authors: Närhi, Anu, Fernandes, Andrea, Toiviainen‐Salo, Sanna, Harris, Jessica, McInerney‐Leo, Aideen, Lazarus, Syndia, Avela, Kristiina, Duncan, Emma L.
Format: Article
Language:English
Subjects:
Alleles
Biomarkers
Carpal Bones - abnormalities
Carpal Bones - pathology
DNA Mutational Analysis
DNA sequencing
Family
Fibrosarcoma
focal segmental glomerulosclerosis
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Genotypes
Hajdu-Cheney Syndrome - diagnosis
Hajdu-Cheney Syndrome - genetics
Hajdu-Cheney Syndrome - surgery
Humans
Kidney transplantation
MafB Transcription Factor - genetics
Male
MCTO
Mosaicism
multicentric carpotarsal osteolysis
Mutation
Osteolysis
Pedigree
Penetrance
Phenotype
Phenotypes
Radiography
Sequence Analysis, DNA
v‐maf musculoaponeurotic fibrosarcoma oncogene ortholog B (MAFB)
Young Adult
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Summary:Multicentric carpotarsal osteolysis (MCTO) is an autosomal dominant condition characterized by carpal–tarsal abnormalities; over half of affected individuals also develop renal disease. MCTO is caused by mutations of MAFB; however, there is no clear phenotype–genotype correlation. We describe the first reported family of variable MCTO phenotype due to mosaicism: the proband had classical skeletal features and renal involvement due to focal segmental glomerulosclerosis (FSGS), and the father had profound renal impairment due to FSGS, necessitating kidney transplantation. Mosaicism was first suspected in this family due to unequal allele ratios in the sequencing chromatograph of the initial blood sample of proband's father and confirmed by sequencing DNA extracted from the father's hair, collected from different bodily parts. This case highlights the need for a high index of clinical suspicion to detect low‐level parental mosaicism, as well as a potential role for MAFB mutation screening in individuals with isolated FSGS.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.62257