LETTER TO JMG

Alport syndrome and mental retardation: clinical and genetic dissection of the contiguous gene deletion syndrome in Xq22.3 (ATS-MR)

I Meloni¹, F Vitelli¹, L Pucci², R B Lowry³, R Tonlorenzi⁴, E Rossi⁵, M Ventura⁶, G Rizzoni⁷, C E Kashtan⁸, B Pober⁹, A Renieri¹

¹ Department of Medical Genetics, University of Siena, Italy
² Department of Paediatrics, University of Siena, Italy
³ Department of Medical Genetics, Alberta Children's Hospital, Calgary, Canada
⁴ TIGEM, Milan, Italy
⁵ Biol Genetics, Genetics Med, University of Pavia, Italy
⁶ Istituto di Genetica, University of Bari, Italy
⁷ Ospedale Bambin Gesù, Roma, Italy
⁸ Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA
⁹ Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA

Correspondence to:
Correspondence to:
Dr A Renieri, Department of Medical Genetics, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy;
renieri@unisi.it

Keywords: Alport syndrome; mental retardation; Xq22.3

Abbreviations: ATS, Alport syndrome; MR, mental retardation; ATS-MR, Alport syndrome and mental retardation; ATS-DL, Alport syndrome and diffuse leiomyomatosis; AMME, Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis

X linked Alport syndrome (ATS, OMIM 301050) is a hereditary glomerulonephritis resulting from either point mutations or intragenic deletions of the COL4A5 gene encoding the 5 chain of type IV collagen.^1–3 Contiguous gene syndromes are phenotypically complex disorders associated with the deletion of multiple adjacent genes. There are several examples of such syndromes on the X chromosome.^{4, 5} Until recently, the only known contiguous gene syndrome involving the COL4A5 gene was Alport syndrome and diffuse leiomyomatosis (ATS-DL, OMIM 308940),^6–9 in which the deletion extends towards the centromere to include the first two exons of the adjacent COL4A6 gene. In 1998, we described a new Xq22.3 contiguous gene syndrome which we named AMME (OMIM 300194) because of the distinctive features observed in affected males: Alport syndrome (A), mental retardation (M), midface hypoplasia (M), and elliptocytosis (E).¹⁰ After the original publication, clinical re-evaluation of the family showed alterations of cardiac rhythm and morphology . . . [Full text of this article]

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