Whole exome sequencing identified a novel truncation mutation in the NHS gene associated with Nance-Horan syndrome.
BACKGROUND
Nance-Horan syndrome (NHS) is an X-linked inheritance disorder characterized by bilateral congenital cataracts, and facial and dental dysmorphism. This disorder is caused by mutations in the NHS gene. However, NHS may be difficult to detect in individuals with subtle facial dysmorphism and dental abnormalities in whom congenital cataracts are the primary clinical manifestations.


METHODS
In this study, we present a three-generation family with NHS. Whole exome sequencing was performed to determine the potential pathogenic variant in the proband. Further validation was explored with Sanger sequencing in 9 of the available individuals of the family and additional 200 controls.


RESULTS
A novel truncation mutation in gene NHS (c.C4449G, p.Tyr1483Ter) was found in the proband, who presented with a long-narrow face, prominent nose and large anteverted pinnae ear, screw-driver like incisors, mild mulberry like molars, one missing maxillary second molar and malocclusion. We found this mutation was detected in 2 male patients and 4 female carriers in the family. However, the mutation was never detected in the control subjects.


CONCLUSIONS
In conclusion, we identified a novel truncation mutation in the NHS gene, which might associate with NHS. Our review on the NHS studies illustrated that NHS has significantly clinical heterogeneity. And NHS mutations in the NHS-affected individuals typically result in premature truncation of the protein. And the new mutation revealed in this study would highlight the understanding of the causative mutations of NHS.
['Ling|Chao|C|', 'Sui|Ruifang|R|', 'Yao|Fengxia|F|', 'Wu|Zhihong|Z|', 'Zhang|Xue|X|0000-0002-8297-9931', 'Zhang|Shuyang|S|']
D000293:Adolescent D000328:Adult D044466:Asians D002386:Cataract D005260:Female D056726:Genetic Association Studies D040181:Genetic Diseases, X-Linked D020022:Genetic Predisposition to Disease D006801:Humans D008297:Male D008565:Membrane Proteins D008875:Middle Aged D009154:Mutation D009687:Nuclear Proteins D014071:Tooth Abnormalities D000073359:Whole Exome Sequencing
Nance-Horan syndrome Congenital cataract NHS mutation Hereditary