| Autor: |
Starosta RT; Division of Genetics and Genomic Medicine, Department of Pediatrics, 7548Washington University in Saint Louis, Saint Louis Children's Hospital, Washington University in Saint Louis, Saint Louis, Missouri.; Department of Pediatrics, 7548Washington University in Saint Louis, Washington University in Saint Louis, St. Louis Children's Hospital, Saint Louis, Missouri., Granadillo JL; Division of Genetics and Genomic Medicine, Department of Pediatrics, 7548Washington University in Saint Louis, Saint Louis Children's Hospital, Washington University in Saint Louis, Saint Louis, Missouri., Patel KR; Department of Pathology and Immunology, Texas Children's Hospital, Houston, Texas., Finegold MJ; Baylor College of Medicine, Houston, Texas., Stoll J; Department of Pediatrics, 7548Washington University in Saint Louis, Washington University in Saint Louis, St. Louis Children's Hospital, Saint Louis, Missouri., Kulkarni S; Department of Pediatrics, 7548Washington University in Saint Louis, Washington University in Saint Louis, St. Louis Children's Hospital, Saint Louis, Missouri. |
| Abstrakt: |
We report a newborn who presented with multiple limb and facial anomalies, endocrine disorders, and progressively worsening low-GGT cholestasis. A liver biopsy revealed hepatocellular cholestasis with giant cell transformation. Immunohistochemical staining revealed complete absence of BSEP protein compared to control liver. A large 2q24-32.2 deletion leading to loss of 78 OMIM genes. Multiple structural anomalies, epilepsy and endocrine anomalies have been described with hemizygous loss of these genes. This deletion also resulted in complete heterozygous deletion of ABCB11 , which encodes the bile salt export pump (BSEP). Genetic analysis did not reveal any pathogenic variants, deletions, or duplications in the other ABCB11 allele. A heterozygous variant in NR1H4, which causes the autosomal recessive progressive familial intrahepatic cholestasis type 5, was also detected. The possible explanations for the PFIC type 2 phenotype in heterozygous loss of ABCB11 include genetic modifiers or di-genic disease with a compound ABCB11 deletion and an NR1H4 missense variant; or undetected pathogenic variants in the other ABCB11 or NR1H4 alleles. |
