Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2022
A Homozygous Missense Variant in Hedgehog Acyltransferase (HHAT) Gene Associated with 46,XY Gonadal Dysgenesis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Mazen Inas, Kamel Alaa, McElreavey Kenneth, Bashamboo Anu, Elaidy Aya, Abdel-Hamid Mohamed S
Аннотация
INTRODUCTION: Disorders of gonadal development represent a clinically and genetically heterogeneous group of DSD, and the etiology in many cases remains unknown, indicating that our knowledge of factors controlling sex determination is still limited.
METHODS: We describe a 46,XY DSD patient from Egypt. The patient was reared as female, born to consanguineous parents, and was referred to us at the age of 5 years because of ambiguous genitalia. On examination, the girl was microcephalic (head circumference -3 SD), but her height and weight were normal for her age and sex.
RESULTS: Exome sequencing identified a homozygous variant in the hedgehog acyltransferase (HHAT) gene, which encodes an enzyme that is required for multimerization and signaling potency of the hedgehog secreted proteins. The variant is a novel homozygous missense change c.1329C>A (p.N443K), located within transmembrane domain 9, which segregated with the phenotype in the family.
DISCUSSION/CONCLUSION: Our results expand the phenotypic spectrum associated with HHAT variants to include 46,XY gonadal dysgenesis and reinforce the role of exome sequencing in unraveling new genes that play a pivotal role in sexual development.
METHODS: We describe a 46,XY DSD patient from Egypt. The patient was reared as female, born to consanguineous parents, and was referred to us at the age of 5 years because of ambiguous genitalia. On examination, the girl was microcephalic (head circumference -3 SD), but her height and weight were normal for her age and sex.
RESULTS: Exome sequencing identified a homozygous variant in the hedgehog acyltransferase (HHAT) gene, which encodes an enzyme that is required for multimerization and signaling potency of the hedgehog secreted proteins. The variant is a novel homozygous missense change c.1329C>A (p.N443K), located within transmembrane domain 9, which segregated with the phenotype in the family.
DISCUSSION/CONCLUSION: Our results expand the phenotypic spectrum associated with HHAT variants to include 46,XY gonadal dysgenesis and reinforce the role of exome sequencing in unraveling new genes that play a pivotal role in sexual development.