**Please Note**:

**This test has been performed for research purposes only** and has not been NATA accredited in our laboratory.

Validation by Sanger sequencing has not been performed on clinically significant or novel detected variants and should be considered by the referring clinician.

**Result:** A mutation in a gene known or predicted to be associated with decreased platelet counts and/ or function has been identified. A second variant of uncertain significance has also been identified.

**DNA variants**: Variant 1: *MYH9*, Heterozygous, c.287C>T (p.Ser96Leu), Exon 2, rs121913657, **pathogenic.**

Variant 2: *NBEAL2*, Heterozygous, c.6178C>T (p.Arg2060Cys), exon37, **uncertain significance.**

**Previously described:** Variant 1: Yes (rs121913657)

Variant 2: No.

**Interpretation:** A heterozygous 287C-T transition in the MYH9 gene, resulting in a ser96-toleu (S96L) substitution, has been predicted to disturb the helical region of the protein resulting in MYH9- related disorder (Epstein syndrome).

The pathogenicity of variant 2 is uncertain as information regarding this mutation is not available in the reported literature. Note that the classification of variants of uncertain/ unknown significance may change over time if additional information on these conditions becomes available in the reported literature.

**References:** Arrondel C, et al. Expression of the non-muscle myosin heavy chain IIA in the human kidney and screening for MYH9 mutations in Epstein and Fechtner syndromes. J Am Soc Nephrol 2002;13: 65–74.

Utsch B, et al. Bladder exstrophy and Epstein type congenital macrothrombocytopenia: evidence for a common cause? (Letter) Am J Med Genet 2006;140A:2251–3.

Kunishima S, et al. Immunofluorescence analysis of neutrophil non-muscle myosin heavy chain-A in MYH9 disorders: association of subcellular localization with MYH9 mutations. Lab Invest 2003;83:115–22.

**Recommendations**: The pathogenicity of detected candidate variants should be validated independently by Sanger sequencing. Where necessary, the functional significance of these variants should be confirmed independently by appropriate biological assays to replicate the phenotype of this patient.

MYH9-related disorders have an autosomal dominant inheritance. Genetic counselling is recommended for this individual and their family. Family screening may be appropriate after appropriate genetic counselling.
