Skeletal dysplasia

Gene: NEPRO

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 3:01 p.m. | Last Modified: 26 Sep 2024, 3:01 p.m.

Panel Version: 6.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

The 'new-gene-name' tag has been added to this gene as the official HGNC gene symbol for NEPRO is RMP64.

Created: 28 Apr 2025, 11:27 a.m. | Last Modified: 28 Apr 2025, 11:27 a.m.

Panel Version: 7.42

Comment on list classification: There are four unrelated cases reported with three different homozygous variants in NEPRO gene. Three unrelated cases were of Arabic/ partial Arabic descent, while the fourth case from India. The evidence available is sufficient enough to promote the rating to green in the next GMS review.

Created: 17 Jan 2024, 10:52 a.m. | Last Modified: 17 Jan 2024, 10:52 a.m.

Panel Version: 4.38

PMID:26633546 reported a sister and brother among 31 Saudi Arabian families studied with skeletal dysplasia and homozygous missense variant in NEPRO gene (p.Arg49Cys).

PMID:29620724 reported the same homozygous NEPRO variant (p.Arg49Cys) in two brothers of Arab descent with skeletal dysplasia. The disorder is identical to phenotypes reported in PMID:26633546 and haplotype analysis confirmed the founder nature of the variant.

PMID:31250547 reported a 13-year-old Indian girl with a different homozygous missense variant (p.Leu145Phe) and with severe short stature and skeletal dysplasia with sparse scalp hair and skin and joint laxity. Her second-cousin parents were heterozygous for the same variant.

PMID:37294112 reported a 7-year-old girl from an Arabic-speaking community in Eastern Africa with Anauxetic dysplasia 3 and another homozygous NEPRO variant (p.Arg94Cys). She was born to consanguineous parents, who reported that their shared ancestor was of Arab descent. This patient presented with clinically relevant features not previously described in ANXD3: atlantoaxial subluxation, extensive dental anomalies, and a sagittal suture craniosynostosis resulting in scaphocephaly.

This gene has been associated with relevant phenotypes in OMIM (MIM #618853), but not in Gene2Phenotype.

Created: 17 Jan 2024, 10:39 a.m. | Last Modified: 17 Jan 2024, 10:48 a.m.

Panel Version: 4.35

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Anauxetic dysplasia 3, OMIM:618853

Publications

• 26633546
• 29620724
• 31250547
• 37294112

I don't know

PMIDs 26633546, 29620724: 2 families with the same homozygous missense variant, haplotype analysis confirmed the founder nature of the variant. PMID 31250547: 1 family with homozygous novel missense All 5 affected individuals have severe short stature, brachydactyly, skin laxity, joint hypermobility, and joint dislocations. They also have short metacarpals, broad middle phalanges, and metaphyseal irregularities. No functional studies.
Sources: Literature

Created: 10 May 2021, 10:30 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Anauxetic dysplasia 3, MIM618853

Publications

• 26633546
• 29620724
• 31250547