Entry - #618095 - INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 63; MRT63 - OMIM

 
ICD+
# 618095

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 63; MRT63


Alternative titles; symbols

MENTAL RETARDATION, AUTOSOMAL RECESSIVE 63


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number 		Inheritance Phenotype
mapping key 		Gene/Locus Gene/Locus
MIM number
5q32 ?Intellectual developmental disorder, autosomal recessive 63 618095 AR 3 CAMK2A 114078
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
GROWTH
Other
- Poor overall growth
MUSCLE, SOFT TISSUES
- Hypotonia, axial
NEUROLOGIC
Central Nervous System
- Delayed psychomotor development, severe
- Intellectual disability, severe
- Inability to walk
- Absence of speech
- Myoclonic seizures
- Spasticity
MISCELLANEOUS
- One consanguineous Jordanian family has been reported (last curated August 2018)
MOLECULAR BASIS
- Caused by mutation in the calcium/calmodulin-dependent protein kinase II-alpha gene (CAMK2A, 114078.0006)
▲ Close
Intellectual developmental disorder, autosomal recessive - PS249500 - 70 Entries
Location Phenotype Inheritance Phenotype
mapping key 		Phenotype
MIM number 		Gene/Locus Gene/Locus
MIM number
1p36.32 Intellectual developmental disorder, autosomal recessive 77 AR 3 619988 CEP104 616690
1p34.1 Intellectual developmental disorder, autosomal recessive 12 AR 3 611090 ST3GAL3 606494
1p21.1-p13.3 Intellectual developmental disorder, autosomal recessive 4 AR 2 611107 MRT4 611107
1p13.3 Intellectual developmental disorder, autosomal recessive 60 AR 3 617432 TAF13 600774
1p13.3 Intellectual developmental disorder, autosomal recessive 48 AR 3 616269 SLC6A17 610299
1q24.3 Glycosylphosphatidylinositol biosynthesis defect 16 AR 3 617816 PIGC 601730
1q31.1 ?Intellectual developmental disorder, autosomal recessive 79 AR 3 620393 TPR 189940
1q32.1 Intellectual developmental disorder, autosomal recessive 65 AR 3 618109 KDM5B 605393
1q43 Intellectual developmental disorder, autosomal recessive 47 AR 3 616193 FMN2 606373
2q11.2 ?Intellectual developmental disorder, autosomal recessive 52 AR 3 616887 LMAN2L 609552
2q22.1 Intellectual developmental disorder, autosomal recessive 51 AR 3 616739 HNMT 605238
2q31.1 Intellectual developmental disorder, autosomal recessive 72 AR 3 618665 METTL5 618628
3p26.2 Intellectual developmental disorder, autosomal recessive 2 AR 3 607417 CRBN 609262
3q12.3 Intellectual developmental disorder, autosomal recessive 69 AR 3 618383 ZBTB11 618181
3q25.32 Intellectual developmental disorder, autosomal recessive 70 AR 3 618402 RSRC1 613352
3q26.2-q26.31 Intellectual developmental disorder, autosomal recessive 54 AR 3 617028 TNIK 610005
4q12-q13.1 Intellectual developmental disorder, autosomal recessive 31 AR 2 614329 MRT31 614329
4q26 Intellectual developmental disorder, autosomal recessive 1 AR 3 249500 PRSS12 606709
4q27-q28.2 Intellectual developmental disorder, autosomal recessive 29 AR 2 614333 MRT29 614333
5p15.31 Intellectual developmental disorder, autosomal recessive 5 AR 3 611091 NSUN2 610916
5q32 ?Intellectual developmental disorder, autosomal recessive 63 AR 3 618095 CAMK2A 114078
5q33.1 Intellectual developmental disorder, autosomal recessive 46 AR 3 616116 NDST1 600853
5q33.2 ?Intellectual developmental disorder, autosomal recessive 76 AR 3 619931 GRIA1 138248
6p12.2-q12 Intellectual developmental disorder, autosomal recessive 24 AR 2 614345 MRT24 614345
6q12-q15 Intellectual developmental disorder, autosomal recessive 30 AR 2 614342 MRT30 614342
6q16.3 Intellectual developmental disorder, autosomal recessive 81 3 620700 ASCC3 614217
6q16.3 Intellectual developmental disorder, autosomal recessive 6 AR 3 611092 GRIK2 138244
6q23.2 Intellectual developmental disorder, autosomal recessive 18, with or without epilepsy AR 3 614249 MED23 605042
6q26-q27 Intellectual developmental disorder, autosomal recessive 28 AR 2 614347 MRT28 614347
7q34 Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly AR 3 620653 CASP2 600639
8p22 Intellectual developmental disorder, autosomal recessive 7 AR 3 611093 TUSC3 601385
8p12 Intellectual developmental disorder, autosomal recessive 39 AR 3 615541 TTI2 614426
8q21.13 Intellectual developmental disorder, autosomal recessive 59 AR 3 617323 IMPA1 602064
8q24.12 Intellectual developmental disorder, autosomal recessive 40 AR 3 615599 TAF2 604912
8q24.3 Intellectual developmental disorder, autosomal recessive 13 AR 3 613192 TRAPPC9 611966
9p23-p13.3 Intellectual developmental disorder, autosomal recessive 16 AR 2 614208 MRT16 614208
9p13.3 Intellectual developmental disorder, autosomal recessive 61 AR 3 617773 RUSC2 611053
9q34.3 Rafiq syndrome AR 3 614202 MAN1B1 604346
10p12.31 Intellectual developmental disorder, autosomal recessive 82 3 620779 NSUN6 617199
10q21.2 Intellectual developmental disorder, autosomal recessive 37 AR 3 615493 ANK3 600465
10q26.12 Intellectual developmental disorder, autosomal recessive 78 AR 3 620237 WDR11 606417
11p15.5 Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly AR 3 619827 PIDD1 605247
11p15.4 Intellectual developmental disorder, autosomal recessive 67 AR 3 618295 EIF3F 603914
11p13-q14.1 Intellectual developmental disorder, autosomal recessive 23 AR 2 614344 MRT23 614344
11q22.3 Intellectual developmental disorder, autosomal recessive 71 AR 3 618504 ALKBH8 613306
12p13.32 Intellectual developmental disorder, autosomal recessive 66 AR 3 618221 C12orf4 616082
12q13.11-q15 Intellectual developmental disorder, autosomal recessive 25 AR 2 614346 MRT25 614346
12q22 Intellectual developmental disorder, autosomal recessive 34, with variant lissencephaly AR 3 614499 CRADD 603454
12q23.3 Intellectual developmental disorder, autosomal recessive 43 AR 3 615817 WASHC4 615748
14q11.2-q12 Intellectual developmental disorder, autosomal recessive 9/26 AR 2 611095 MRT9 611095
14q31.3 Intellectual developmental disorder, autosomal recessive 56 AR 3 617125 ZC3H14 613279
15q13.1 Intellectual developmental disorder, autosomal recessive 38 AR 3 615516 HERC2 605837
15q24.1 ?Intellectual developmental disorder, autosomal recessive 50 AR 3 616460 EDC3 609842
15q24.3 Intellectual developmental disorder, autosomal recessive 64 AR 3 618103 LINGO1 609791
15q26.3 Intellectual developmental disorder, autosomal recessive 27 AR 3 614340 LINS1 610350
16p12.2-q12.1 Intellectual developmental disorder, autosomal recessive 10/20 AR 2 611096 MRT10 611096
16q24.2 ?Intellectual developmental disorder, autosomal recessive 45 AR 3 615979 FBXO31 609102
17p13.2-p13.1 Intellectual developmental disorder, autosomal recessive 33 AR 2 614341 MRT33 614341
17q21.31-q22 Intellectual developmental disorder, autosomal recessive 35 AR 2 615162 MRT35 615162
17q25.1 Intellectual developmental disorder, autosomal recessive 44 AR 3 615942 METTL23 615262
18q12.2 Intellectual developmental disorder, autosomal recessive 58 AR 3 617270 ELP2 616054
19p13.3 Intellectual developmental disorder, autosomal recessive 74 AR 3 617169 APC2 612034
19p13.3 Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies AR 3 615286 ADAT3 615302
19p13.13 Intellectual developmental disorder, autosomal recessive 68 AR 3 618302 TRMT1 611669
19p13.12 Intellectual developmental disorder, autosomal recessive 3 AR 3 608443 CC2D1A 610055
19p13.12 Intellectual developmental disorder, autosomal recessive 14 AR 3 614020 TECR 610057
19q13.2-q13.3 Intellectual developmental disorder, autosomal recessive 11 AR 2 611097 MRT11 611097
19q13.32 Intellectual developmental disorder, autosomal recessive 41 AR 3 615637 KPTN 615620
19q13.42 Intellectual developmental disorder, autosomal recessive 57 AR 3 617188 MBOAT7 606048
20p11.23 Intellectual developmental disorder, autosomal recessive 73 AR 3 619717 NAA20 610833
▲ Close

▼ TEXT

A number sign (#) is used with this entry because of evidence that autosomal recessive intellectual developmental disorder-63 (MRT63) is caused by homozygous mutation in the CAMK2A gene (114078) on chromosome 5q32. One such family has been reported.

▼ Clinical Features

Chia et al. (2018) reported 2 sibs, born of consanguineous parents from Jordan, with a neurodevelopmental disorder characterized by global developmental delay, severe intellectual disability, and seizures with EEG abnormalities suggestive of myoclonic seizures. At ages 11 and 14 years, the patients were unable to walk or speak, but had eye contact. They also exhibited axial hypotonia with appendicular spasticity. The patients had poor overall growth, but did not have dysmorphic features. Brain imaging was normal.


▼ Inheritance

The transmission pattern of MRT63 in the family reported by Chia et al. (2018) was consistent with autosomal recessive inheritance.


▼ Molecular Genetics

In 2 sibs, born of consanguineous parents from Jordan, with MRT63, Chia et al. (2018) identified a homozygous missense mutation in the CAMK2A gene (H477Y; 114078.0006). The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient-derived fibroblasts that were reprogrammed into neurons showed significantly reduced spontaneous spikes and firing rate compared to controls, consistent with a loss of function. Additional in vitro functional expression studies in HEK293 cells showed that the mutant protein was expressed at lower levels compared to wildtype, and impaired oligomerization and assembly of the multimeric holoenzyme. The findings were consistent with a partial loss of function, which could explain why the heterozygous parents were unaffected. Transfection of the mutation into unc43-null C. elegans failed to rescue neuronal and synaptic defects, also consistent a loss of function.


▼ REFERENCES

  1. Chia, P. H., Zhong, F. L., Niwa, S., Bonnard, C., Utami, K. H., Zeng, R., Lee, H., Eskin, A., Nelson, S. F., Xie, W. H., Al-Tawalbeh, S., El-Khateeb, M., Shboul, M., Pouladi, M. A., Al-Raqad, M., Reversade, B. A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability. eLife 7: e32451, 2018. Note: Electronic Article. [PubMed: 29784083, images, related citations] [Full Text]


Creation Date:
Cassandra L. Kniffin : 08/23/2018
Edit History:
carol : 04/07/2022
carol : 08/29/2018
carol : 08/28/2018
ckniffin : 08/23/2018

# 618095

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 63; MRT63


Alternative titles; symbols

MENTAL RETARDATION, AUTOSOMAL RECESSIVE 63


ORPHA: 178469;   DO: 0081224;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number 		Inheritance Phenotype
mapping key 		Gene/Locus Gene/Locus
MIM number
5q32 ?Intellectual developmental disorder, autosomal recessive 63 618095 Autosomal recessive 3 CAMK2A 114078

TEXT

A number sign (#) is used with this entry because of evidence that autosomal recessive intellectual developmental disorder-63 (MRT63) is caused by homozygous mutation in the CAMK2A gene (114078) on chromosome 5q32. One such family has been reported.

Clinical Features

Chia et al. (2018) reported 2 sibs, born of consanguineous parents from Jordan, with a neurodevelopmental disorder characterized by global developmental delay, severe intellectual disability, and seizures with EEG abnormalities suggestive of myoclonic seizures. At ages 11 and 14 years, the patients were unable to walk or speak, but had eye contact. They also exhibited axial hypotonia with appendicular spasticity. The patients had poor overall growth, but did not have dysmorphic features. Brain imaging was normal.


Inheritance

The transmission pattern of MRT63 in the family reported by Chia et al. (2018) was consistent with autosomal recessive inheritance.


Molecular Genetics

In 2 sibs, born of consanguineous parents from Jordan, with MRT63, Chia et al. (2018) identified a homozygous missense mutation in the CAMK2A gene (H477Y; 114078.0006). The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient-derived fibroblasts that were reprogrammed into neurons showed significantly reduced spontaneous spikes and firing rate compared to controls, consistent with a loss of function. Additional in vitro functional expression studies in HEK293 cells showed that the mutant protein was expressed at lower levels compared to wildtype, and impaired oligomerization and assembly of the multimeric holoenzyme. The findings were consistent with a partial loss of function, which could explain why the heterozygous parents were unaffected. Transfection of the mutation into unc43-null C. elegans failed to rescue neuronal and synaptic defects, also consistent a loss of function.


REFERENCES

  1. Chia, P. H., Zhong, F. L., Niwa, S., Bonnard, C., Utami, K. H., Zeng, R., Lee, H., Eskin, A., Nelson, S. F., Xie, W. H., Al-Tawalbeh, S., El-Khateeb, M., Shboul, M., Pouladi, M. A., Al-Raqad, M., Reversade, B. A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability. eLife 7: e32451, 2018. Note: Electronic Article. [PubMed: 29784083] [Full Text: https://doi.org/10.7554/eLife.32451]


Creation Date:
Cassandra L. Kniffin : 08/23/2018

Edit History:
carol : 04/07/2022
carol : 08/29/2018
carol : 08/28/2018
ckniffin : 08/23/2018



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OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2024 Johns Hopkins University.

NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2024 Johns Hopkins University.
Printed: April 25, 2024