Dystrophia canthorum in Waardenburg syndrome with a novel MITF mutation

AIM:To reveal a novel MITF gene mutation in Waardenburg syndrome(WS),which is an autosomal dominant inherited neurogenic disorder that consists of various degrees of sensorineural deafness and pigmentary abnormalities in the eyes,hair and skin.METHODS:The genetic analysis of the Chinese family was conducted by whole-exome sequencing,then the results were confirmed by Sanger sequencing.RESULTS:WS is classified into type I to IV,which are identified by the W index,clinical characteristics and additional features.The MITF gene mostly accounts for WS type II.In this study,a de novo heterozygous mutation in the MITF gene,c.638 A>G in exon 7,was identified in the patient diagnosed with WS type I features,as the W index was 2.17(over 2.10),with dystrophia canthorum,congenital bilateral profound hearing loss,bilateral heterochromia irides,premature greying of the hair,and excessive freckling on the face at birth.She also underwent refractive errors and esotropia,reduced pigmentation of the choroid and visible choroid vessels.The mutation was not found in previous studies or mutation databases.CONCLUSION:The novel mutation in the MITF gene,which altered the protein in amino acids 213 from the glutamic acid to glycine,is the genetic pathological cause for WS features in the patient.Those characteristics of this family revealed a novel genetic heterogeneity of MITF in WS,which expanded the database of MITF mutations and offered a possible in correcting the W index value of WS in distinct ethnicities.Moreover,ocular symptoms should be emphasized in all types of WS patients.

Case of Waardenburg Shah syndrome in a family with review of literature

Waardenburg syndrome is a rare disease characterized by sensorineural deafness in association with pigmentary defects. Depending on additional symptoms, WS have been classified into four types.Waardenburg syndrome type 4, also called as Waardenburg Shah Syndrome is a very rare congenital disorder with astounding variable clinical expression, characterized by pigmentary abnormalities of the hair(A white forelock of hair, premature graying) and pigmentary changes of the iris such as heterochromia or homochromia irides, sensorineural deafness and Hirschsprung disease. Three genes have been bestowed so far in consociation with EDNRB, EDN3, and SOX10 genes. The pattern of inheritance is multifarious with the SOX10 mutation affiliation with autosomal dominant inheritance whereas the EDNRB and EDN3 genes are passed down in an autosomally recessive pattern.