Primordial Dwarfism via the LARP7 Gene

Primordial dwarfism (PD) is characterized by severe intrauterine and postnatal growth retardation that includes Seckel Syndrome, Silver-Russell Syndrome, Microcephalic Osteodysplastic Primordial Dwarfism types I/III, II and Meier-Gorlin Syndrome (Khetarpal et al. 2016). LARP7-related Primordial Dwarfism is called Alazami Syndrome. In addition to severe intrauterine and postnatal growth retardation, patients with Alazami Syndrome may also present with intellectual disability. Other features include abnormal skeletal and skin defects, such as scoliosis, thickened skin, as well as involuntary movements of the upper limbs (Alazami et al. 2012; Ling et al. 2016).

LARP7-related primordial dwarfism is an autosomal recessive disorder. LARP7 protein is a key component of 7SK small nuclear ribonucleoprotein (snRNP) complex and plays a key role during embryonic development (Najmabadi H. et al. 2011; Alazami et al. 2012; Ling et al. 2016). To date, only a few truncating pathogenic variants have been reported, either in the compound heterozygous state or in the homozygous state (Alazami et al. 2012; Ling et al., 2016, Human Gene Mutation Database).

The mutation detection rate by sequencing should be high, because the four known unique pathogenic variants are nonsense, small duplication, and small deletion. However, due to limited publications, clinical sensitivity is not yet known.

This test provides full coverage of all coding exons of the LARP7 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).