title: Peripheral neuropathy and 46XY gonadal dysgenesis: a heterogeneous entity.
abstract: Gonadal dysgenesis with normal male karyotype (46XY) is a sexual differentiation disorder. So far three patients have been reported presenting the association of 46XY gonadal dysgenesis with peripheral neuropathy. Examination of sural nerves revealed minifascicle formation in two of them. In one patient, a mutation was found in desert hedgehog homolog (Drosophila), a gene important in gonadal differentiation and peripheral nerve development. We studied neuropathological and molecular genetic aspects of a patient with 46XY gonadal dysgenesis and peripheral neuropathy. Examination of a sural nerve biopsy specimen revealed an axonal neuropathy with pronounced axonal loss, limited signs of axonal regeneration and no minifascicle formation. A normal male karyotype was found (46XY) without micro-deletions in the Y chromosome. No mutations were found in the sex determining region Y gene, peripheral myelin protein 22, Myelin Protein Zero, Gap-Junction protein Beta 1, Mitofusin 2 or desert hedgehog homolog. The absence of minifascicle formation and the absence of a mutation in desert hedgehog homolog in this patient with gonadal dysgenesis and peripheral neuropathy expand the clinical and genetic heterogeneity of this rare entity.
authors.affiliation: Neurogenetics group, VIB Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerpen, Belgium.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baets
authors.forename: Ines
authors.initials: I
authors.lastname: Dierick
authors.forename: Chantal Ceuterick-de
authors.initials: CC
authors.lastname: Groote
authors.forename: Jenneke van den
authors.initials: Jv
authors.lastname: Ende
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.forename: Karin
authors.initials: K
authors.lastname: Geens
authors.forename: Wim
authors.initials: W
authors.lastname: Robberecht
authors.forename: Eva
authors.initials: E
authors.lastname: Nelis
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.forename: Peter De
authors.initials: PD
authors.lastname: Jonghe
mesh_terms: D001369:Axons / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D015897:Comorbidity; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005836:Genitalia, Female / Q000002:abnormalities; D005838:Genotype; D006061:Gonadal Dysgenesis, 46,XY / Q000150:complications* / Q000235:genetics*; D006066:Gonads / Q000002:abnormalities; D006801:Humans; D007621:Karyotyping; D008875:Middle Aged; D009431:Neural Conduction / Q000235:genetics; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D012733:Sex Differentiation / Q000235:genetics; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014855:Wallerian Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology