Likely inborn error of metabolism

Gene: LBR

Green List (high evidence)

Comment on mode of inheritance: Pelger-Huet anomaly, seen in numerous carriers of heterozygous LBR variants, does not usually cause any symptoms and thus it is considered a benign condition. There is also one patient reported with a het LBR variant and Reynolds syndrome. However, the variant is present in homozygous state in gnomAD, and its significance is hard to determine. Hence, the mode of inheritance should be changed to 'BIALLELIC, autosomal or pseudoautosomal' on this panel. An expert_review tag has been added to ensure GMS agreement with this demotion.

Created: 9 Sep 2026, 2:08 p.m. | Last Modified: 9 Sep 2026, 2:13 p.m.

Panel Version: 9.32

MONOALLELIC CASES
Reynolds syndrome:
PMID: 20522425 Gaudy-Marqueste et al., 2010
76-year-old Caucasian woman with Reynolds syndrome (primary biliary cholangitis and limited cutaneous systemic sclerosis). She was het for LBR c.1114C>T; p.Arg372Cys - AF in gnomAD is 0.0002441, with 2 homozygotes reported.

Pelger-Huet anomaly (PHA) is considered to be a benign disorder in most instances, as individuals with PHA are typically healthy. It is an inherited blood condition in which the nuclei of several types of white blood cells (neutrophils and eosinophils) have unusual shape and structure. See PMID: 12118250 Hoffmann et al., 2002 and PMID: 19468205 Speeckaert et al., 2009.

LBR is associated with AR regressive spondylometaphyseal dysplasia (Moderate, 2023) and AR Greenberg dysplasia (Moderate, 2023) in ClinGen. LBR is linked to AR Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly, AR Greenberg skeletal dysplasia, AD Pelger-Huet anomaly, and putatively linked to AD ?Reynolds syndrome in OMIM (accessed 9th Sept 2026).

Created: 9 Sep 2026, 2:03 p.m. | Last Modified: 9 Sep 2026, 2:09 p.m.

Panel Version: 9.32

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pelger-Huet anomaly, OMIM:169400; Greenberg skeletal dysplasia, OMIM:215140; Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly, OMIM:618019; ?Reynolds syndrome, OMIM:613471

Publications

• 12118250
• 19468205
• 20522425

Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Greenberg skeletal dysplasia 215140. At least 15 variants have been reported, in 5 unrelated cases of Pelger-Huet anomaly 169400, 3 unrelated cases of Pelger-Huet anomaly with mild skeletal anomalies 618019, 5 unrelated cases of Greenberg skeletal dysplasia 215140 and in a single case of ?Reynolds syndrome 613471.

Created: 15 Aug 2019, 1:13 p.m. | Last Modified: 15 Aug 2019, 1:13 p.m.

Panel Version: 1.160

Comment on phenotypes: Greenberg skeletal dysplasia (Disorders of sterol biosynthesis);Unexplained skeletal dysplasia;Fetal hydrops

Created: 15 Aug 2019, 12:38 p.m. | Last Modified: 15 Aug 2019, 12:38 p.m.

Panel Version: 1.158