Alternative titles; symbols
SNOMEDCT: 720982007; ORPHA: 86818; DO: 0111860;
Cytogenetic location: Xq22.3 Genomic coordinates (GRCh38) : X:104,500,001-109,400,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| Xq22.3 | AMME complex | 300194 | 4 |
A number sign (#) is used with this entry because the AMME complex is a contiguous gene deletion syndrome on chromosome Xq22-q23.
The AMME complex is an X-linked contiguous gene deletion syndrome with features of Alport syndrome (see 301050), impaired intellectual development, midface hypoplasia, and elliptocytosis in affected males (summary by Meloni et al., 2002).
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.
Moyses-Oliveira et al. (2018) reported 2 maternal half-sibs (patients 4 and 5) with impaired intellectual development and facial features including a prominent forehead, flat face, and malar flattening. Patient 4 also had failure to thrive, short stature, and skeletal alterations. Patient 5 also had psychomotor delay and elliptocytosis. Neither patient had kidney abnormalities.
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).
Moyses-Oliveira et al. (2018) reported 2 maternal half sibs (patients 4 and 5) with AMME complex. The patients were hemizygous for a 414-kb deletion at chromosome Xq23, which included the AMMECR1 and RGAG1 (300965) genes. The sibs' mother, maternal aunt, and maternal grandmother were heterozygous for the deletion.
Jonsson, J. J., Renieri, A., Gallagher, P. G., Kashtan, C. E., Cherniske, E. M., Bruttini, M., Piccini, M., Vitelli, F., Ballabio, A., Pober, B. R. Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis: a new X linked contiguous gene deletion syndrome? J. Med. Genet. 35: 273-278, 1998. [PubMed: 9598718] [Full Text: https://doi.org/10.1136/jmg.35.4.273]
Meloni, I., Muscettola, M., Raynaud, M., Longo, I., Bruttini, M., Moizard, M.-P., Gomot, M., Chelly, J., des Portes, V., Fryns, J.-P., Ropers, H.-H., Magi, B., Bellan, C., Volpi, N., Yntema, H. G., Lewis, S. E., Schaffer, J. E., Renieri, A. FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation. Nature Genet. 30: 436-440, 2002. [PubMed: 11889465] [Full Text: https://doi.org/10.1038/ng857]
Meloni, I., Vitelli, F., Pucci, L., Lowry, R. B., Tonlorenzi, R., Rossi, E., Ventura, M., Rizzoni, G., Kashtan, C. E., Pober, B., Renieri, A. Alport syndrome and mental retardation: clinical and genetic dissection of the contiguous gene deletion syndrome in Xq22.3 (ATS-MR). J. Med. Genet. 39: 359-365, 2002. [PubMed: 12011158] [Full Text: https://doi.org/10.1136/jmg.39.5.359]
Moyses-Oliveira, M., Giannuzzi, G., Fish, R. J., Rosenfeld, J. A., Petit, F., Soares, M. D., Kulikowski, L. D., Di-Battista, A., Zamariolli, M., Xia, F., Liehr, T., Kosyakova, N., and 23 others. Inactivation of AMMECR1 is associated with growth, bone, and heart alterations. Hum. Mutat. 39: 281-291, 2018. [PubMed: 29193635] [Full Text: https://doi.org/10.1002/humu.23373]
Piccini, M., Vitelli, F., Bruttini, M., Pober, B. R., Jonsson, J. J., Villanova, M., Zollo, M., Borsani, G., Ballabio, A., Renieri, A. FACL4, a new gene encoding long-chain acyl-CoA synthetase 4, is deleted in a family with Alport syndrome, elliptocytosis, and mental retardation. Genomics 47: 350-358, 1998. [PubMed: 9480748] [Full Text: https://doi.org/10.1006/geno.1997.5104]
Robson, W. L. M., Lowry, R. B., Leung, A. K. C. X-linked recessive nephritis with mental retardation, sensorineural hearing loss, and macrocephaly. Clin. Genet. 45: 314-317, 1994. [PubMed: 7923864] [Full Text: https://doi.org/10.1111/j.1399-0004.1994.tb04039.x]
Vitelli, F., Piccini, M., Caroli, F., Franco, B., Malandrini, A., Pober, B., Jonsson, J., Sorrentino, V., Renieri, A. Identification and characterization of a highly conserved protein absent in the Alport syndrome (A), mental retardation (M), midface hypoplasia (M), and elliptocytosis (E) contiguous gene deletion syndrome (AMME). Genomics 55: 335-340, 1999. [PubMed: 10049589] [Full Text: https://doi.org/10.1006/geno.1998.5666]