Missense variants in the TRPM7 α-kinase domain are associated with recurrent pediatric acute liver failure.

Background: Pediatric acute liver failure (PALF) is a rare and life-threatening condition. In up to 50% of PALF cases, the underlying etiology remains unknown during routine clinical testing. This lack of knowledge complicates clinical management and liver transplantation decisions.

The Recurrent E-Cadherin (CDH1) Mutation c.760G>A Causes Orofacial Clefts but Does Not Predispose to Hereditary Cancer.

: Congenital, non-syndromic orofacial clefts (CL/P) are infrequently monogenic in etiology. However, heterozygous pathogenic germline variants were reported in a few non-syndromic CL/P families, as well as in one syndromic form of CL/P: the blepharocheilodontic syndrome. encodes epithelial cadherin (E-cadherin), and close to 300 different pathogenic variants are listed in the ClinVar mutation database.

PERCC1 -Related Congenital Enteropathy.

A total of 14 patients are known with the nonsyndromic enteropathy caused by biallelic deletions (∆L and ∆S) or truncating mutations affecting PERCC1 or its adjacent regulatory region. PERCC1 is so far in gnomAD only annotated in the GRCh38 reference sequence. Parenteral nutrition is required throughout childhood and often in adolescence.

Steatotic liver disease associated with 2,4-dienoyl-CoA reductase 1 deficiency.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered multifactorial with a number of predisposing gene polymorphisms known.

Methods: The occurrence of MASLD in 7 and 10 year old siblings, one without classical risk factors and one with type 2 diabetes suggested a monogenic etiology and prompted next-generation sequencing. Exome sequencing was performed in the proband, both parents and both siblings.