BICD2 mutational analysis in hereditary spastic paraplegia and hereditary motor and sensory neuropathy

Abstract

Introduction: Mutations in the BICD2 gene are causative for an autosomal dominant form of spinal muscular atrophy (SMALED2). Further, BICD2 mutations have been implicated in hereditary spastic paraplegia (HSP), but only very few such patients have been described. In this report we aimed to investigate the frequency of BICD2 mutations in patients with HSP and hereditary motor and sensory neuropathy (HMSN) who were negative for the most common known genetic causes. Methods: The cohorts comprised 171 HSP and 189 HMSN patients. Mutational analysis was performed with high‐resolution melting analysis followed by Sanger sequencing. Results: In both cohorts, we found no known or likely pathogenic mutations in the BICD2 gene. Discussion: BICD2 mutations appear rather unlikely to cause a phenotype of HMSN and are a very rare cause of the HSP phenotype. Muscle Nerve 59:484–486, 2019

A homozygous loss-of-function variant in BICD2 is associated with lissencephaly and cerebellar hypoplasia

“…Dominant missense variants in the Bicaudal D2 Drosophila homolog 2 ( BICD2 ) gene were initially described in autosomal dominant lower extremity-predominant spinal muscular atrophy 2 (SMALED2A;MIM#609797) [ 1 ] and its prenatal onset form (SMALED2B, MIM #618291) [ 2 ]. Subsequent reports linked heterozygous BICD2 variants to hereditary spastic paraplegia [ 3 ] and developmental brain malformations [ 4 , 5 ]. Recently, a homozygous BICD2 variant was reported in a girl with Cohen-Like syndrome and abnormal gyral pattern [ 6 ].…”

Homozygous variant in COQ7 causes autosomal recessive hereditary spastic paraplegia

“…Vice versa, it was also possible for some patients could exhibit a dominance of HSP along with dHMN. Additionally, at least 16 subtypes of complex HSP could also exhibit spasticity combined with motor neuropathy, such as SPG17 and SPG38, 10 , 11 among others. Their clinical manifestations were very similar to those of patients with COQ7 variants.…”

Integrating protein networks and machine learning for disease stratification in the Hereditary Spastic Paraplegias

“…The list of HSP test seeds (n=17) is: ACO2 ( Bouwkamp et al., 2018 ), ALS2 ( Simone et al., 2018 ), BICD2 ( Kropatsch et al., 2019 ), CCDC50, CCT5 ( Bouhouche et al., 2006 ), EXOSC3 ( Blackstone, 2018a ), GAD1 ( Lo Giudice et al., 2014 ), HACE1 ( Akawi et al., 2015 ), IFIH1 ( Liu et al., 2019 ), KCNA2 ( Helbig et al., 2016 ), KIDINS220 ( Zhao et al., 2019 ), LYST ( Shimazaki et al., 2014 ), MT-ATP6 ( Verny et al., 2011 ), MT-CO3 ( Blackstone, 2018b ), MT-ND4 ( Clarencon et al., 2006 ), RETREG1 ( Ilgaz Aydinlar et al., 2014 ) and SELENOI ( Ahmed et al., 2017 )…”