Khan et al. (2012) identified a novel NHS mutation (c.2232delG) in a family with seven affected members with congenital or infantile cataract and facial dysmorphism.  Sixteen family members were studied; two affected and six asymptomatic females, five affected and three asymptomatic males.  The six asymptomatic females were aged between 4-35 years old.  Four had posterior Y-suture centered lens opacities and exhibited facial dysmorphism, while the fifth asymptomatic girl had scattered fine punctate lens opacities, while the sixth had clear lenses.  The NHS mutation was also found in the four asymptomatic girls with Y-centered lens opacities but not the other two asymptomatic girls or in the three asymptomatic males (who had clear lenses).

Chograni et al (2011) studied a Tunisian family affected with Nance Horan Syndrome.  Linkage analysis in this family localized the disease region to the Xp22.32-p11.21 region with a 2-point LOD score of 0.90.  This region contained the NHS gene, which was considered to be the most likely causative gene.  Sequencing of all eight exons and the flanking regions revealed the presence of four variants in this gene in this family.  One of these was a novel missense mutation, c.1989C>T (p.P551S) that was not found in 78 control chromosomes and was also found to be conserved across eight species.  This variation was found in hemizygous condition in all three affected male siblings, and in heterozygous condition in their unaffected mother.  It was not present in other unaffected siblings, confirming it as a disease-causing co-segregating mutation.  In addition, the authors also found out a reported polymorphism, c.4293C>T (p.L1319F), a reported UTR-SNP, c.7422C>T, and a novel UTR-SNP, c.8239T>A.  The c.1989C>T mutation was predicted to contribute to the appearance of a novel low complexity serine rich region with a tandem-repeat insertion.  This was the first report of a missense mutation in the NHS gene leading to Nance-Horam Syndrome; all other reported mutations being nonsense or frameshift mutations.  Interestingly, the phenotype in this family was reported to be less severe than that reported in other families with truncating mutations.