Arthrogryposis
Gene: BICD2Comment on list classification: Promoted BICD2 from Red to Green based on recent literature evidence and Green review by Zerin Hyder (Genomics England Clinical Team). Sufficient unrelated cases of AMC for inclusion on panel.Created: 29 Nov 2019, 2:07 p.m. | Last Modified: 29 Nov 2019, 2:07 p.m.
Panel Version: 2.107
PMID:27751653 (Ravenscroft et al., 2016) report two unrelated probands (a German male and a boy from a Welsh mother and NZ/European father) that presented in utero with reduced fetal movement. Both cases had arthrogryposis multiplex congenita (AMC) and hypotonia diagnosed at birth . The same missense de novo variant in BICD2 (p.Arg694Cys) was present in both probands.
PMID:29274205 (Ahmed et al., 2018) report a stillborn female fetus (case 4) with pterygia and arthrogryposis with a heterozygous likely-pathogenic variant in BICD2. Phenotypes included an abnormal fetal position with fixed limbs, hydrops fetalis and polyhydramnios. A heterozygous p.Asn700Lys variant in BICD2 was revealed. However, compound het variants of unknown significance in AGRN were also identified, so the authors can not be certain that BICD2 is the causative variant.
PMID:28635954 (Storbeck et al., 2017) describe 3 individuals of independent families with severe arthrogryposis multiplex congenita (AMC), respiratory insufficiency, and early lethality caused by three BICD2 variants (p.Arg694Cys, p.Gln194Arg and p.Cys542Trp, 2 of which are proven to be de novo). They also describe an asymptomatic woman with subclinical findings with the previously described p.(Thr703Met) variant.
PMID: 30054298. In 2 unrelated patients with muscular atrophy and arthrogryposis Koboldt et al. (2018) identified a de novo heterozygous c.1636_1638delAAT variant in the BICD2 gene. The mutation, which was found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but protein modeling indicated that the variant is within a region that interacts with the molecular kinesin motor and that the mutation would alter protein structure.Created: 29 Nov 2019, 2:02 p.m. | Last Modified: 29 Nov 2019, 2:03 p.m.
Panel Version: 2.104
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant 615290; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291
Publications
Recent paper indicates a wide phenotypic spectrum for BICD2 from arthrogryposis to asymptomatic with variable expressivity within families.
European Journal of Human Genetics (2017) 25, 1040–1048
Phenotypic extremes of BICD2-opathies: from lethal,
congenital muscular atrophy with arthrogryposis to
asymptomatic with subclinical features
Markus Storbeck1,2,3, Beate Horsberg Eriksen4, Andreas Unger5, Irmgard Hölker1,2,3, Ingvild Aukrust6,
Lilian A Martínez-Carrera1,2,3, Wolfgang A Linke5, Andreas Ferbert7, Raoul Heller1, Matthias Vorgerd8,
Gunnar Houge6 and Brunhilde Wirth*,1,2,3Created: 10 Aug 2017, 12:11 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2A, 615290; autosomal dominant, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 to arthrogryposis multiplex congenita; Spinal muscular atrophy, lower extremity-predominant, 2A, 615290; autosomal dominant, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291
Gene: bicd2 has been classified as Green List (High Evidence).
Publications for gene: BICD2 were set to 28635954
Mode of inheritance for gene: BICD2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 to Spinal muscular atrophy, lower extremity-predominant, 2A, 615290; autosomal dominant, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291
Phenotypes for gene: BICD2 were changed from to Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291
Publications for gene: BICD2 were set to
16th Jan 2016: This gene panel was extensively revised with the addition of 101 green genes and review by Alice Gardham. Due to this extensive change to the panel, the decision was made to promote it to the next major version, version 2.
This gene has been classified as Red List (Low Evidence).
BICD2 was created by ellenmcdonagh
BICD2 was added to Arthrogryposispanel. Sources: Expert list