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Expanding the MYBPC1 phenotypic spectrum: a novel homozygous mutation causes arthrogryposis multiplex congenita
Author(s) -
Ekhilevitch N.,
Kurolap A.,
OzLevi D.,
Mory A.,
Hershkovitz T.,
Ast G.,
Mandel H.,
Baris H.N.
Publication year - 2016
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12707
Subject(s) - arthrogryposis multiplex congenita , arthrogryposis , missense mutation , genetics , phenotype , nonsense mutation , exome sequencing , biology , muscle contracture , camptodactyly , exon , consanguinity , mutation , gene , anatomy
Arthrogryposis multiplex congenita ( AMC ) is characterized by heterogeneous nonprogressive multiple joint contractures appearing at birth. We present a consanguineous Israeli‐Druze family with several members presenting with AMC . A variable intra‐familial phenotype and pected autosomal recessive inheritance prompted molecular diagnosis by whole‐exome sequencing. Variant analysis focused on rare homozygous changes, revealed a missense variant in MYBPC1 , NM_002465:c. 556G >A (p. E286K ), affecting the last nucleotide of Exon 8. This novel variant was not observed in the common variant databases and co‐segregated as expected within the extended family. MYBPC1 encodes a slow skeletal muscle isoform, essential for muscle contraction. Heterozygous mutations in this gene are associated with distal arthrogryposis types 1b and 2, whereas a homozygous nonsense mutation is implicated in one family with lethal congenital contractural syndrome 4. We present a novel milder MYBPC1 homozygous phenotype.