Limb-Girdle Muscular Dystrophy and Distal Myopathy
Gene: NEB
Although there are three unrelated cases reported with cleft palate in literature and a case reported with bifid uvula in the DECIPHER project, clefting has not been consistently reported as a phenotype in patients with biallelic NEB variants and is not fully penetrant in at least one family with clefting. Hence, this gene should be added with amber rating in the 'clefting disorders' panel.
PMID:12207937 - A 9 month-old boy from one of five families affected by nemaline myopathy and reported with NEB variants had cleft palate. This patient was homozygous for 1-bp deletion in exon 184, which was also found in the mother, whereas no DNA was available from father.
PMID:21798101 - Two siblings were reported with severe arthrogryposis multiplex congenital and were identified with compound heterozygous variants in NEB gene (c.1152 + 1G > T & c.11318_11319del), of which one patient had cleft palate.
PMID:33376055 - A male foetus of consanguineous parents with a severe congenital syndrome characterized by arthrogryposis detected at 13 weeks of gestation had cleft palate and was identified with homozygous splice-site NEB variant (c.19,102-1G>T).
DECIPHER databse - Of 10 patients with biallelic (compound heterozygous or homozygous) sequence variants in NEB gene reported in DECIPHER database, one patient with compound heterozygous NEB variants had bifid uvula.
Cleft palate has been associated as one of the clinical presentations of Arthrogryposis multiplex congenita 6 (MIM #619334) in OMIM.Created: 14 Aug 2023, 3:27 p.m. | Last Modified: 14 Aug 2023, 3:27 p.m.
Panel Version: 1.1111
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Arthrogryposis multiplex congenita 6, OMIM:619334
Publications
Distal myopathy has been reported as a presenting feature, mainly in cases with biallelic missense variants.
Sources: LiteratureCreated: 7 Jun 2023, 5:59 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
distal myopathy MONDO:0018949
Publications
Variants in this GENE are reported as part of current diagnostic practice
More than 5 unrelated families reported with AMC6, severe end of NEB-associated disorder with prenatal presentation.Created: 1 Jun 2021, 1:07 a.m. | Last Modified: 1 Jun 2021, 1:07 a.m.
Panel Version: 0.7735
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Arthrogryposis multiplex congenita 6, MIM# 619334
Publications
PMID: 25205138: all variants are autosomal recessive, most commonly compound heterozygous
- early-onset distal myopathy without nemaline bodies
- a distal form of NM
- core-rod myopathy with generalized muscle weakness
- childhood-onset distal myopathy with rods and cores
- fetal akinesia/lethal multiple pterygium syndrome.
Mutational hotspot at donor splice sites of intron 32 (c.3255+1 and c.3255+2Created: 9 Jul 2020, 4:13 a.m. | Last Modified: 9 Jul 2020, 4:13 a.m.
Panel Version: 0.3281
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Nemaline myopathy 2, autosomal recessive 256030
Publications
Gene: neb has been classified as Green List (High Evidence).
Gene: neb has been classified as Green List (High Evidence).
gene: NEB was added gene: NEB was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature Mode of inheritance for gene: NEB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEB were set to 21724397; 17525139; 33458580; 25205138 Phenotypes for gene: NEB were set to distal myopathy MONDO:0018949 Review for gene: NEB was set to GREEN gene: NEB was marked as current diagnostic