Spastic paraplegia-47 is an autosomal recessive neurodegenerative disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity and severe mental retardation with poor or absent speech development (summary by Abou Jamra et al., 2011).
Abou Jamra et al. (2011) reported a consanguineous Israeli Arab family (ID01) in which 3 sibs had severe mental retardation and spasticity. All presented at birth with microcephaly and muscular hypotonia, which later developed to hypertonia. Physical examination ... Abou Jamra et al. (2011) reported a consanguineous Israeli Arab family (ID01) in which 3 sibs had severe mental retardation and spasticity. All presented at birth with microcephaly and muscular hypotonia, which later developed to hypertonia. Physical examination showed hyperreflexia, spastic paraplegia, and an inability to walk unaided. All had a severe cognitive deficit, marked speech delay, and adaptive impairment. Other features included high palate, wide nasal bridge, short stature, hyperlaxity, genu recurvatum, pes planus, and a waddling gait. They had stereotypic laughter and markedly shy character. None had seizures, vision or hearing impairments, or any anomalies of inner organs. Blumkin et al. (2011) reported 2 sibs, born of consanguineous Arab parents, with a severe neurodegenerative disorder beginning in infancy. The patients had delayed psychomotor development, mental retardation, and spastic paraplegia with increased tone in the lower limbs, hyperreflexia, and extensor plantar responses. Both had febrile seizures in early childhood. One child had dysarthria at age 5.5 years, and the other showed spastic tongue protrusion and jaw opening with hypersalivation. Brain imaging of both patients showed thinning of the corpus callosum and periventricular white matter changes. Dysmorphic features were not observed, although 1 had microcephaly.
By linkage analysis followed by candidate gene sequencing of an Israeli Arab family with autosomal recessive mental retardation and spasticity, Abou Jamra et al. (2011) identified a homozygous truncating mutation in the AP4B1 gene (607245.0001). The authors concluded ... By linkage analysis followed by candidate gene sequencing of an Israeli Arab family with autosomal recessive mental retardation and spasticity, Abou Jamra et al. (2011) identified a homozygous truncating mutation in the AP4B1 gene (607245.0001). The authors concluded that AP4-complex-mediated vesicular trafficking plays a crucial role in brain development and function. In 2 sibs, born of consanguineous Arab parents, with SPG47, Bauer et al. (2012) identified a homozygous truncating mutation in the AP4B1 gene (607245.0002). The mutation was found by exome sequencing of the candidate region on chromosome 1p13-p12 identified by linkage analysis (Blumkin et al., 2011). Bauer et al. (2012) noted the phenotypic similarities to the patients reported by Abou Jamra et al. (2011).