#615942
Table of Contents
A number sign (#) is used with this entry because autosomal recessive intellectual developmental disorder-44 (MRT44) is caused by homozygous mutation in the METTL23 gene (615262) on chromosome 17q25.
Reiff et al. (2014) reported a consanguineous kindred of Yemeni origin in which 7 individuals had intellectual disability and dysmorphic features. Detailed clinical features were available for 3 patients. Each had delayed psychomotor development, with walking at age 1.5 years, and moderate to severe cognitive impairment; 1 had autistic features. Two had controlled seizures. Brain imaging performed on 1 patient was normal. Dysmorphic features included flat occiput, large eyes, depressed nasal bridge, short, upturned nose, long philtrum, thin lips, and incomplete syndactyly. One patient had a cleft uvula and submucosal cleft palate.
Bernkopf et al. (2014) reported 2 unrelated consanguineous families with autosomal recessive impaired intellectual development. Four Austrian sibs had delayed psychomotor development apparent after the first year of life but maintained a high level of functioning, with independent activities of daily living. The patients also had flat feet and 3 had prominent maxillae, a feature also present in a milder form in the mother. None had seizures. Brain imaging of 1 patient showed possibly increased volume of the subcallosal gray matter and decreased delineation of the basal ganglia. Two Pakistani sisters had similar features; the brain MRI of 1 sister showed decreased delineation of the basal ganglia region. Bernkopf et al. (2014) noted that the neurologic phenotype was milder in their patients compared to that reported by Reiff et al. (2014).
Smaili et al. (2020) reported Moroccan brother and sister with mildly impaired intellectual development and dysmorphic features. The brother had speech delay at age 7 years, and the sister had absent speech at age 6 years. Dysmorphic features seen in both patients included macrocephaly, scaphocephaly, prominent eyes, low-set ears, short upturned nose, bilateral fifth finger clinodactyly, and flat feet. The authors noted the similarity of the dysmorphic features between their patients and those previously reported, suggesting that this is a distinct clinical entity.
By genomewide linkage analysis of a consanguineous Yemeni family with autosomal recessive intellectual disability, Reiff et al. (2014) found linkage to a 14.2-cM region on chromosome 17q25.1-q25.3 between markers rs820388 and rs4313838 (maximum lod score of 6.01).
In affected members of a Yemeni family with autosomal recessive intellectual developmental disorder-44, Reiff et al. (2014) identified a homozygous truncating mutation in the METTL23 gene (615262.0001). The mutation was found using homozygosity mapping followed by exome sequencing of genes within the candidate region.
In affected members of 2 unrelated consanguineous families with a mild form of nonsyndromic MRT44, Bernkopf et al. (2014) identified 2 different homozygous truncating mutations in the METTL23 gene (615262.0002 and 615262.0003). The mutation in the first family was found by linkage analysis and exome sequencing of the candidate region. Overexpression of the mutant proteins resulted in the formation of protein aggregates of isoforms 1 and 2 in the cytoplasm. However, Bernkopf et al. (2014) suggested loss of protein function as a pathogenic mechanism.
In 2 Moroccan sibs with MRT44, Smaili et al. (2020) identified a homozygous frameshift mutation in the METTL23 gene (615262.0004). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents.
Bernkopf, M., Webersinke, G., Tongsook, C., Koyani, C. N., Rafiq, M. A., Ayaz, M., Muller, D., Enzinger, C., Aslam, M., Naeem, F., Schmidt, K., Gruber, K., Speicher, M. R., Malle, E., Macheroux, P., Ayub, M., Vincent, J. B., Windpassinger, C., Duba, H.-C. Disruption of the methyltransferase-like 23 gene METTL23 causes mild autosomal recessive intellectual disability. Hum. Molec. Genet. 23: 4015-4023, 2014. [PubMed: 24626631, images, related citations] [Full Text]
Reiff, R. E., Ali, B. R., Baron, B., Yu, T. W., Ben-Salem, S., Coulter, M. E., Schubert, C. R., Hill, R. S., Akawi, N. A., Al-Younes, B., Kaya, N., Evrony, G. D., and 10 others. METTL23, a transcriptional partner of GABPA, is essential for human cognition. Hum. Molec. Genet. 23: 3456-3466, 2014. [PubMed: 24501276, images, related citations] [Full Text]
Smaili, W., Elalaoui, S. C., Zrhidri, A., Raymond, L., Egea, G., Taoudi, M., Mouatassim, S. E. L., Sefiani, A., Lyahyai, J. Exome sequencing revealed a novel homozygous METTL23 gene mutation leading to familial mild intellectual disability with dysmorphic features. Europ. J. Med. Genet. 63: 103951, 2020. [PubMed: 32439618, related citations] [Full Text]
Alternative titles; symbols
ORPHA: 88616; DO: 0081208;
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
---|---|---|---|---|---|---|
17q25.1 | Intellectual developmental disorder, autosomal recessive 44 | 615942 | Autosomal recessive | 3 | METTL23 | 615262 |
A number sign (#) is used with this entry because autosomal recessive intellectual developmental disorder-44 (MRT44) is caused by homozygous mutation in the METTL23 gene (615262) on chromosome 17q25.
Reiff et al. (2014) reported a consanguineous kindred of Yemeni origin in which 7 individuals had intellectual disability and dysmorphic features. Detailed clinical features were available for 3 patients. Each had delayed psychomotor development, with walking at age 1.5 years, and moderate to severe cognitive impairment; 1 had autistic features. Two had controlled seizures. Brain imaging performed on 1 patient was normal. Dysmorphic features included flat occiput, large eyes, depressed nasal bridge, short, upturned nose, long philtrum, thin lips, and incomplete syndactyly. One patient had a cleft uvula and submucosal cleft palate.
Bernkopf et al. (2014) reported 2 unrelated consanguineous families with autosomal recessive impaired intellectual development. Four Austrian sibs had delayed psychomotor development apparent after the first year of life but maintained a high level of functioning, with independent activities of daily living. The patients also had flat feet and 3 had prominent maxillae, a feature also present in a milder form in the mother. None had seizures. Brain imaging of 1 patient showed possibly increased volume of the subcallosal gray matter and decreased delineation of the basal ganglia. Two Pakistani sisters had similar features; the brain MRI of 1 sister showed decreased delineation of the basal ganglia region. Bernkopf et al. (2014) noted that the neurologic phenotype was milder in their patients compared to that reported by Reiff et al. (2014).
Smaili et al. (2020) reported Moroccan brother and sister with mildly impaired intellectual development and dysmorphic features. The brother had speech delay at age 7 years, and the sister had absent speech at age 6 years. Dysmorphic features seen in both patients included macrocephaly, scaphocephaly, prominent eyes, low-set ears, short upturned nose, bilateral fifth finger clinodactyly, and flat feet. The authors noted the similarity of the dysmorphic features between their patients and those previously reported, suggesting that this is a distinct clinical entity.
By genomewide linkage analysis of a consanguineous Yemeni family with autosomal recessive intellectual disability, Reiff et al. (2014) found linkage to a 14.2-cM region on chromosome 17q25.1-q25.3 between markers rs820388 and rs4313838 (maximum lod score of 6.01).
In affected members of a Yemeni family with autosomal recessive intellectual developmental disorder-44, Reiff et al. (2014) identified a homozygous truncating mutation in the METTL23 gene (615262.0001). The mutation was found using homozygosity mapping followed by exome sequencing of genes within the candidate region.
In affected members of 2 unrelated consanguineous families with a mild form of nonsyndromic MRT44, Bernkopf et al. (2014) identified 2 different homozygous truncating mutations in the METTL23 gene (615262.0002 and 615262.0003). The mutation in the first family was found by linkage analysis and exome sequencing of the candidate region. Overexpression of the mutant proteins resulted in the formation of protein aggregates of isoforms 1 and 2 in the cytoplasm. However, Bernkopf et al. (2014) suggested loss of protein function as a pathogenic mechanism.
In 2 Moroccan sibs with MRT44, Smaili et al. (2020) identified a homozygous frameshift mutation in the METTL23 gene (615262.0004). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents.
Bernkopf, M., Webersinke, G., Tongsook, C., Koyani, C. N., Rafiq, M. A., Ayaz, M., Muller, D., Enzinger, C., Aslam, M., Naeem, F., Schmidt, K., Gruber, K., Speicher, M. R., Malle, E., Macheroux, P., Ayub, M., Vincent, J. B., Windpassinger, C., Duba, H.-C. Disruption of the methyltransferase-like 23 gene METTL23 causes mild autosomal recessive intellectual disability. Hum. Molec. Genet. 23: 4015-4023, 2014. [PubMed: 24626631] [Full Text: https://doi.org/10.1093/hmg/ddu115]
Reiff, R. E., Ali, B. R., Baron, B., Yu, T. W., Ben-Salem, S., Coulter, M. E., Schubert, C. R., Hill, R. S., Akawi, N. A., Al-Younes, B., Kaya, N., Evrony, G. D., and 10 others. METTL23, a transcriptional partner of GABPA, is essential for human cognition. Hum. Molec. Genet. 23: 3456-3466, 2014. [PubMed: 24501276] [Full Text: https://doi.org/10.1093/hmg/ddu054]
Smaili, W., Elalaoui, S. C., Zrhidri, A., Raymond, L., Egea, G., Taoudi, M., Mouatassim, S. E. L., Sefiani, A., Lyahyai, J. Exome sequencing revealed a novel homozygous METTL23 gene mutation leading to familial mild intellectual disability with dysmorphic features. Europ. J. Med. Genet. 63: 103951, 2020. [PubMed: 32439618] [Full Text: https://doi.org/10.1016/j.ejmg.2020.103951]
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