RESUMO
Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH.
Assuntos
Transtornos Testiculares 46, XX do Desenvolvimento Sexual , Cromossomos Humanos Par 22/química , Doenças Desmielinizantes/genética , Doença de Hirschsprung/genética , Falência Renal Crônica/genética , Doença de Pelizaeus-Merzbacher/genética , Síndrome de Waardenburg/genética , Negro ou Afro-Americano , Duplicação Cromossômica , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/etnologia , Doenças Desmielinizantes/patologia , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/etnologia , Doença de Hirschsprung/patologia , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etnologia , Falência Renal Crônica/patologia , Masculino , Doença de Pelizaeus-Merzbacher/diagnóstico , Doença de Pelizaeus-Merzbacher/etnologia , Doença de Pelizaeus-Merzbacher/patologia , Fatores de Transcrição SOXE/genética , Síndrome de Waardenburg/diagnóstico , Síndrome de Waardenburg/etnologia , Síndrome de Waardenburg/patologiaRESUMO
The authors report a case of a premature male neonate born at 25.3 weeks gestational age weighing 605 grams with septo-optic dysplasia (SOD) and a heterozygous mutation in TUBA1A c.715A>C, a critical gene for microtubules, who developed asymmetric and aggressive posterior retinopathy of prematurity (ROP). This report presents a novel mutation associated with SOD and proposes that optic nerve hypoplasia may have potentiated a severe ROP phenotype. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:629-632.].