1. A patient with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and severe hypoganglionosis associated with a novel SOX10 mutation
- Author
-
Akira Takei, Tomohiro Aoyama, Ken Inoue, Yudai Goto, Akimitu Watanabe, Keiko Suzuki, Kouji Masumoto, Masaharu Hayashi, Tetsuo Hori, Masatoshi Imamura, Takashi Enokizono, Kentaro Shirai, Yuko Akutsu, and Tatsuyuki Ohto
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Biopsy ,DNA Mutational Analysis ,SOX10 ,Frameshift mutation ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Humans ,Medicine ,Waardenburg Syndrome ,Hirschsprung Disease ,Frameshift Mutation ,Genetic Association Studies ,Genetics (clinical) ,Hypopigmentation ,Enterocolitis ,SOXE Transcription Factors ,business.industry ,Waardenburg syndrome ,Skull ,Brain ,Facies ,Infant ,Exons ,Hypoganglionosis ,medicine.disease ,Immunohistochemistry ,Magnetic Resonance Imaging ,Hypotonia ,Ganglion ,Intestines ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,Mutation ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Demyelinating Diseases - Abstract
In this report, we present the case of a female infant with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH) associated with a novel frameshift mutation (c.842dupT) in exon 5, the last exon of SOX10. She had severe hypoganglionosis in the small intestine and entire colon, and suffered from frequent enterocolitis. The persistence of ganglion cells made both the diagnosis and treatment difficult in the neonatal period. She also showed hypopigmentation of the irises, hair and skin, bilateral sensorineural deafness with hypoplastic inner year, severe demyelinating neuropathy with hypotonia, and diffuse brain hypomyelination. The p.Ser282GlnfsTer12 mutation presumably escapes from nonsense-mediated decay and may generate a dominant-negative effect. We suggest that hypoganglionosis can be a variant intestinal manifestation associated with PCWH and that hypoganglionosis and aganglionosis may share the same pathoetiological mechanism mediated by SOX10 mutations.
- Published
- 2018