KLHL7 – PERCHING syndrome

PERCHING syndrome is a rare multisystem developmental disorder inherited in an autosomal recessive manner and caused by biallelic variants in KLHL7 associated with PERCHING syndrome. To date, three unrelated probands have been reported: one African patient with compound heterozygous splice (c.793+5G>C) and frameshift (c.944delG (p.Ser315ThrfsTer23)) variants ((PMID:35670385)), one fetus diagnosed prenatally with a homozygous nonsense variant ((PMID:36217303)), and one Iranian child with a homozygous missense variant c.110T>G (p.Val37Gly) ((PMID:38333279)).

Clinical features across these cases include global developmental delay (HP:0001263), hypotonia (HP:0001252), delayed speech (HP:0000750), enlarged cisterna magna (HP:0002280) and multisystem dysmorphism with neurological, respiratory, gastrointestinal and autonomic dysfunction. All variants were inherited from heterozygous carrier parents without additional affected relatives, and no segregation beyond parental testing has been documented.

Genetic evidence consists of bi-allelic KLHL7 variants identified in three probands: one splice and one frameshift allele in a compound heterozygote ((PMID:35670385)), one homozygous nonsense allele ((PMID:36217303)), and one homozygous missense allele ((PMID:38333279)). Variant classes include splice, frameshift, nonsense and missense alterations. Inheritance is autosomal recessive with limited segregation data. No functional assays or model systems have been reported that directly assess the impact of these variants on PERCHING syndrome pathogenesis.

References

• American journal of medical genetics. Part A • 2022 • PERCHING syndrome: Clinical presentation in the first African patient confirmed by clinical whole genome sequencing. PMID:35670385
• Prenatal diagnosis • 2022 • Prenatal diagnosis of PERCHING syndrome caused by homozygous loss of function variant in the KLHL7 gene. PMID:36217303
• Annals of medicine and surgery • 2024 • PERCHING syndrome caused by variant gene KLHL7 in the first Iranian patient: a case report study. PMID:38333279

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