TY - JOUR
T1 - Clinical and Pathological Features of a Newborn With Compound Heterozygous ANKS6 Variants
AU - Kulkarni, Sakil
AU - Abro, Brooj
AU - Duque Lasio, Maria Laura
AU - Stoll, Janis
AU - Grange, Dorothy K.
AU - He, Mai
N1 - Publisher Copyright:
© 2019, Society for Pediatric Pathology All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - We report a term female infant born to nonconsanguineous parents who presented with renal failure at birth, hypothyroidism, cholestasis, and progressive cardiac dysfunction. Multigene next-generation sequencing panels for cholestasis, cardiomyopathy, and cystic renal disease did not reveal a unifying diagnosis. Whole exome sequencing revealed compound heterozygous pathogenic variants in ANKS6 (Ankyrin Repeat and Sterile Alpha Motif Domain Containing 6), which encodes a protein that interacts with other proteins of the Inv compartment of cilium (NEK8, NPHP2/INVS, and NPHP3). ANKS6 has been shown to be important for early renal development and cardiac looping in animal models. Autopsy revealed cystic renal dysplasia and cardiomyocyte hypertrophy, disarray, and focal necrosis. Liver histology revealed cholestasis and centrilobular necrosis, which was likely a result of progressive cardiac failure. This is the first report of compound heterozygous variants in ANKS6 leading to a nephronopthisis-related ciliopathy-like phenotype. We conclude that pathogenic variants in ANKS6 may present early in life with severe renal and cardiac failure, similar to subjects with variants in genes encoding other proteins in the Inv compartment of the cilium.
AB - We report a term female infant born to nonconsanguineous parents who presented with renal failure at birth, hypothyroidism, cholestasis, and progressive cardiac dysfunction. Multigene next-generation sequencing panels for cholestasis, cardiomyopathy, and cystic renal disease did not reveal a unifying diagnosis. Whole exome sequencing revealed compound heterozygous pathogenic variants in ANKS6 (Ankyrin Repeat and Sterile Alpha Motif Domain Containing 6), which encodes a protein that interacts with other proteins of the Inv compartment of cilium (NEK8, NPHP2/INVS, and NPHP3). ANKS6 has been shown to be important for early renal development and cardiac looping in animal models. Autopsy revealed cystic renal dysplasia and cardiomyocyte hypertrophy, disarray, and focal necrosis. Liver histology revealed cholestasis and centrilobular necrosis, which was likely a result of progressive cardiac failure. This is the first report of compound heterozygous variants in ANKS6 leading to a nephronopthisis-related ciliopathy-like phenotype. We conclude that pathogenic variants in ANKS6 may present early in life with severe renal and cardiac failure, similar to subjects with variants in genes encoding other proteins in the Inv compartment of the cilium.
KW - ANKS6
KW - Inv compartment
KW - cholestasis
KW - cilia
KW - hypertrophic cardiomyopathy
KW - nephronopthisis
UR - http://www.scopus.com/inward/record.url?scp=85074386739&partnerID=8YFLogxK
U2 - 10.1177/1093526619881541
DO - 10.1177/1093526619881541
M3 - Article
C2 - 31635528
AN - SCOPUS:85074386739
SN - 1093-5266
VL - 23
SP - 235
EP - 239
JO - Pediatric and Developmental Pathology
JF - Pediatric and Developmental Pathology
IS - 3
ER -