Skeletal dysplasia
Gene: NEPRO
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
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: LiteratureCreated: 10 May 2021, 10:30 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Anauxetic dysplasia 3, MIM618853
Publications
Tag Q1_24_promote_green tag was added to gene: NEPRO.
Gene: nepro has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: NEPRO were changed from Anauxetic dysplasia 3, MIM618853 to Anauxetic dysplasia 3, OMIM:618853
Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
gene: NEPRO was added gene: NEPRO was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: NEPRO was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEPRO were set to 26633546; 29620724; 31250547 Phenotypes for gene: NEPRO were set to Anauxetic dysplasia 3, MIM618853 Review for gene: NEPRO was set to AMBER