Amme Complex

A number sign (#) is used with this entry because of evidence that the AMME complex is a contiguous gene deletion syndrome.

Clinical Features

Robson et al. (1994) described a family in which 2 brothers and a maternal uncle had mental retardation and macrocephaly in addition to nephritis and sensorineural hearing loss. In one of the brothers, microscopic hematuria and red blood cell casts were first noted at the age of 2.5 years and persisted in subsequent urinalysis. He was treated with peritoneal dialysis from the age of 13 years and died unexpectedly at age 16. The second brother had a craniopharyngioma, which was removed surgically at the age of 17.5 years. The uncle, who had severe mental retardation, died of chronic renal failure at the age of 22 years. The mother of the 2 brothers had persistent microscopic hematuria, as did their maternal grandmother.

Jonsson et al. (1998) described a family with 4 members, a mother, 2 sons, and a daughter, with features of X-linked Alport syndrome. In addition, the 2 males had mental retardation, dysmorphic facies with midface hypoplasia, and elliptocytosis.

Molecular Genetics

Molecular characterization by Jonsson et al. (1998) of their family suggested a submicroscopic deletion of the X chromosome including the COL4A5 gene (303630). Jonsson et al. (1998) proposed that the additional features in the affected males might be due to disruption of genes adjacent to COL4A5 and that the phenotype might represent a contiguous gene deletion syndrome. Piccini et al. (1998) presented evidence that this was a true contiguous gene syndrome involving both the COL4A5 and FACL4 (300157) genes. FACL4 encodes a long-chain acyl-CoA synthetase (Piccini et al., 1998). Vitelli et al. (1999) showed that another gene deleted in this syndrome is AMMECR1 (300195).

Meloni et al. (2002) identified a second family with Alport syndrome and mental retardation, confirmed the existence of a contiguous gene syndrome in Xq22.3, which they called ATS-MR, and characterized the deletion in the 2 ATS-MR families. They compared the extent of deletion between individuals with ATS-MR and individuals with ATS alone to define a critical region for mental retardation of approximately 380 kb, containing 4 candidate genes: FACL, NXT2 (300320), KCNE5 (KCNE1L; 300218), and GUCY2F (300041). Meloni et al. (2002) reported the identification of 2 point mutations, 1 missense and 1 splice site change, in the FACL4 gene in 2 families with nonspecific mental retardation.

Meloni et al. (2002) further characterized the contiguous gene syndrome on Xq22.3 as well as the previously known contiguous gene syndrome in this region, ATS-DL (Alport syndrome and diffuse leiomyomatosis; 308940). Both syndromes involve deletion of COL4A5, but whereas ATS-DL extends centromerically, ATS-MR extends telomerically with respect to the collagen gene. One of the families they studied had been described by Robson et al. (1994).