Aarskog‐Scott syndrome: Confirmation of linkage to the pericentromeric region of the X chromosome

Abstract

Aarskog-Scott syndrome was tentatively mapped to Xq13 on the basis of an X:8 translocation by Bawle et al. [Am J Med Genet 17:595-602, 1984]. A review of the cytogenetics and the use of molecular markers in that family have resulted in revision of the breakpoints of the translocation to Xp 11.2 and 8q11.21 [Glover et al., Hum Mol Genet 2:1717-1718, 1993]. Two families, including one of the two initial families with Aarskog-Scott syndrome [Scott, BD:OAS VII (6): 240-246, 1971], have participated in our study to evaluate the localization of the gene for Aarskog-Scott syndrome to the pericentromeric region of the X chromosome. Using a series of DNA probes, we have been able to confirm linkage to the X chromosome, with multipoint analysis indicating the most likely localization of the gene to be on the proximal short arm.

Clinical variation of Aarskog syndrome in a large family with 2189delA in the FGD1 gene

“…As described before, the facial features in ASS change with age, with hypertelorism becoming less obvious, the forehead becoming less prominent, and the face becoming elongated. The typical morphology of the hands is also less evident, making the clinical diagnosis in adults difficult [Fryns, 1992; Stevenson et al, 1994]. The natural history of two of our patients that were re‐evaluated in adolescence or adulthood is consistent with this observation.…”

Non‐syndromic X‐linked mental retardation associated with a missense mutation (P312L) in the FGD1 gene

“…Aarskog syndrome, which is distinctive in its craniofacial, genital and skeletal manifestations, is widely recognized by clinical geneticists (24–29). Mental retardation is an inconsistent finding and, when present, tends to be mild.…”

Two novel mutations confirm FGD1 is responsible for the Aarskog syndrome

“…The FGDY gene had been mapped to the pericentromeric region of the X chromosome by the observation of an X;8 translocation in an affected mother and son. 5 Porteus et al 6 and Stevenson et al 7 linked the Aarskog gene to Xp11.3-Xq13. Glover et al 8 precisely assigned the breakpoint to Xp11.21 on re-evaluation of the chromosomes in 1993.…”