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A family with partially penetrant multicentric carpotarsal osteolysis due to gonadal mosaicism: First reported case
Author(s) -
Närhi Anu,
Fernandes Andrea,
ToiviainenSalo Sanna,
Harris Jessica,
McInerneyLeo Aideen,
Lazarus Syndia,
Avela Kristiina,
Duncan Emma L.
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62257
Subject(s) - proband , genetics , focal segmental glomerulosclerosis , pathology , germline mosaicism , genetic counseling , biology , medicine , phenotype , endocrinology , kidney , mutation , proteinuria , gene
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.