title: A unique case of female pseudohermaphroditism with 21-hydroxylase deficiency and small supernumerary marker chromosome 7.
abstract: Small supernumerary marker chromosomes (sSMCs) are present in ~2.6x10⁶ individuals worldwide. Concerning their clinical consequences as well as their chromosomal origin and shape, sSMCs are a heterogeneous group of derivative chromosomes; 70% of sSMC carriers are clinically normal. In the present study, we report on a female with mosaicism (45%) of a de novo sSMC derived from chromosome 7, in which the observed clinical signs do not correspond to comparable cases in the literature. She is clinically normal apart from problems in gender determination, a uterus without ovaries and an external penis, pointing overall towards an adrenogenital syndrome (AGS). 21-Hydroxylase deficiency (21-OHD) is the most common cause of AGS. A corresponding analysis for underlying mutations in the CYP21A2 gene revealed a homozygous mutation c.518T>A (p.Ile173Asn) inherited from both non-related parents. Overall, in this study, we report a unique case of female pseudohermaphroditism, classified as a simple virilization form of 21-OHD having an additional minute-shaped chromosome 7 [min(7)(:p11.1->q11.23:)]. Notably, AGS was due to a mutation in the CYP21A2 gene located on chromosome 6. This is a further example that detection of an sSMC does not always resolve the clinical case.
authors: Department of Molecular Biology and Biotechnology, Division of Human Genetics, Atomic Energy Commission of Syria, Damascus, Syria. ascientific@aec.org.sy
authors: Walid
authors: W
authors: Al-Achkar
authors: Abdulsamad
authors: A
authors: Wafa
authors: Manar
authors: M
authors: Assaad
authors: Christian
authors: C
authors: Ehlers
authors: Thomas
authors: T
authors: Liehr
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000201:enzymology* / Q000235:genetics*; D000311:Adrenal Glands / Q000000981:diagnostic imaging / Q000473:pathology; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D020732:Cytogenetic Analysis; D005091:Exons / Q000235:genetics; D019066:Facies; D005260:Female; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D012303:Ring Chromosomes; D013255:Steroid 21-Hydroxylase / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
chemical_list: D005819:Genetic Markers; D013255:Steroid 21-Hydroxylase