TY - JOUR
T1 - LMOD3-associated nemaline myopathy
T2 - Prenatal ultrasonographic, pathologic, and molecular findings
AU - Berkenstadt, Michal
AU - Pode-Shakked, Ben
AU - Barel, Ortal
AU - Barash, Hila
AU - Achiron, Reuven
AU - Gilboa, Yinon
AU - Kidron, Dvora
AU - Raas-Rothschild, Annick
N1 - Publisher Copyright:
© 2017 by the American Institute of Ultrasound in Medicine.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - To describe the prenatal presentation, including ultrasonographic, histologic, and molecular findings, in 2 fetuses affected with LMOD3-related nemaline myopathy. Prenatal ultrasonographic examinations and histopathologic studies were performed on 2 fetuses with evidence of nemaline myopathy. To establish a molecular diagnosis, whole-exome sequencing was pursued for the affected fetuses. Nemaline myopathy is a common form of congenital myopathy manifesting with nonprogressive generalized muscle weakness, hypotonia, and electron-dense protein inclusions in skeletal myofibers. Although clinically, nemaline myopathy can be viewed as a common pathway phenotype, its molecular basis is heterogeneous, with mutations in 11 identified genes implicated in its pathogenesis so far. Whole-exome sequencing revealed that the affected fetuses were compound heterozygous for 2 newly reported pathogenic variants in the LMOD3 gene, which encodes leiomodin 3. To our knowledge, this article is the first report of LMOD3-related nemaline myopathy since the original reported cohort. We provide a detailed description of the prenatal imaging of these affected fetuses, which we hope, in combination with nextgeneration sequencing, may contribute to further diagnosis in additional families.
AB - To describe the prenatal presentation, including ultrasonographic, histologic, and molecular findings, in 2 fetuses affected with LMOD3-related nemaline myopathy. Prenatal ultrasonographic examinations and histopathologic studies were performed on 2 fetuses with evidence of nemaline myopathy. To establish a molecular diagnosis, whole-exome sequencing was pursued for the affected fetuses. Nemaline myopathy is a common form of congenital myopathy manifesting with nonprogressive generalized muscle weakness, hypotonia, and electron-dense protein inclusions in skeletal myofibers. Although clinically, nemaline myopathy can be viewed as a common pathway phenotype, its molecular basis is heterogeneous, with mutations in 11 identified genes implicated in its pathogenesis so far. Whole-exome sequencing revealed that the affected fetuses were compound heterozygous for 2 newly reported pathogenic variants in the LMOD3 gene, which encodes leiomodin 3. To our knowledge, this article is the first report of LMOD3-related nemaline myopathy since the original reported cohort. We provide a detailed description of the prenatal imaging of these affected fetuses, which we hope, in combination with nextgeneration sequencing, may contribute to further diagnosis in additional families.
KW - Arthrogryposis
KW - Genetics
KW - LMOD3
KW - Leiomodin 3
KW - Nemaline myopathy
KW - Paediatrics
UR - http://www.scopus.com/inward/record.url?scp=85055159928&partnerID=8YFLogxK
U2 - 10.1002/jum.14520
DO - 10.1002/jum.14520
M3 - Article
C2 - 29331079
AN - SCOPUS:85055159928
SN - 0278-4297
VL - 37
SP - 1827
EP - 1833
JO - Journal of Ultrasound in Medicine
JF - Journal of Ultrasound in Medicine
IS - 7
ER -