LAS1L-Related Disorders via the LAS1L Gene

LAS1L pathogenic variants have been identified in two families with syndromic X-linked intellectual disability, also referred to as Wilson-Turner Syndrome. Affected individuals in both families had mild to moderate intellectual disability, obesity, speech impairment, and hypogonadism (Hu et al. 2014). In another study, exome sequencing identified a de novo LAS1L variant in an infant with a spinal muscular atrophy with respiratory distress phenotype (SMARD)-like phenotype (Butterfield et al. 2014). The infant presented with distal weakness and primary respiratory failure with mild flexion contractures of the toes and modestly reduced finger extension. To date, no symptomatic female carriers have been reported.

LAS1L-related disorders are inherited in an X-linked recessive manner. To date, missense variants are the only pathogenic variants reported in the LAS1L gene (Human Gene Mutation Database). Recent studies have demonstrated an important role for LAS1L in ribosomal biogenesis. Loss of LAS1L results in p53-depedant cell-cycle arrest, defective pre-rRNA processing and failure to synthesize mature 60S ribosomal subunits (Butterfield et al. 2014).

Clinical sensitivity cannot be estimated because only a small number of patients have been reported. Analytical sensitivity should be high because all reported pathogenic variants thus far are detectable by sequencing.

Thus far, no large deletions or duplications involving the LAS1L gene have been reported.

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the LAS1L gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.