Al-Yahyaee et al. (2006) described two families diagnosed with autosomal recessive hereditary spastic paraplegia.  The first extended family had multiple consanguineous marriages with six affected individuals.  In the second family, the parents were first cousins and had a total of seven children, three of them were affected.  Using linkage analysis for both families, a disease gene location on chromosome 8 between markers D8S1820 and D8S532 (located on 8p12-p11.21) was identified.  Within this interval there were two functional candidate genes, neuregulin and KIF13B.

Anas et al. (2011) described an extended consanguineous Saudi family with five affected members (two siblings and three maternal uncles) with HSP.  Using autozygosity mapping and linkage analysis, a novel 20 kb deletion spanning two protein-coding genes, ERLIN2 and FLJ34378 (a gene of unknown function) were identified in all five patients.  The loss of ERLIN2 initiation exons along with mislocalization of exon 2 was the cause of nullimorphic allele.  The ERLIN2 depletion was strongly associated with HSP patients, while the deletion of FLJ34378 gene may contribute as a modifier effect.

Al-Saif et al. (2012) performed single nucleotide polymorphism arrays for homozygosity mapping for four siblings from the central region of the Arabian Peninsula affected with juvenile primary lateral sclerosis. Homozygous splice junction mutation in intron 7 of the ERLIN2 gene (c.499-1G>T) was identified in all affecteds, resulting in an abnormal splicing of the ERLIN2 transcript and nonsense-mediated decay of ERLIN2 mRNA.

Wakil et al. (2012) analyzed two Hereditary Spastic Paraplegias (HSP) patients belonging to a consanguineous Saudi family.  The patients, a 7-year-old boy and a 19-year-old girl, suffered from early-onset spasticity and weakness of the lower limbs coupled with mild hypertonia of the upper limbs.  The disease also affected their speech and cognitive function.  Their parents were healthy and had two other unaffected children.  Homozygosity mapping was carried out on all members of the family to identify regions homozygous to the affected siblings.  A novel intronic splice acceptor site mutation c.499-1 G>T in intron 7 of the ERLIN2 gene was thus identified.  This mutation was not found in 500 ethnically-matched controls, nor was it seen in the 1000 Genomes or SNP database.  By employing RT-PCR, the study confirmed the insertion of 23 bases retained from the end of intron 7.  This was caused by the activation of a cryptic acceptor splice site.  This 23 base insertion led to the addition of a few faulty amino acids and ultimately resulted in premature termination (p.Q169LfsX 4).