Entry - #620393 - INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 79; MRT79 - OMIM

 
 
# 620393

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 79; MRT79


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number 		Inheritance Phenotype
mapping key 		Gene/Locus Gene/Locus
MIM number
1q31.1 ?Intellectual developmental disorder, autosomal recessive 79 620393 AR 3 TPR 189940
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
HEAD & NECK
Head
- Microcephaly, postnatal (below first percentile)
Face
- Dysmorphic facial features
Eyes
- Deep-set eyes
- Pseudo-strabismus
Nose
- Broad nasal bridge
- Prominent nasal bridge
- Bulbous nasal tip
Mouth
- Thin upper vermilion border
SKELETAL
Limbs
- Hyperextensible joints
Hands
- Long fingers
- Thin fingers
- Fifth finger clinodactyly
SKIN, NAILS, & HAIR
Skin
- Dry skin
- Eczematous skin
NEUROLOGIC
Central Nervous System
- Global developmental delay
- Delayed walking
- Impaired intellectual development, severe
- Ataxic gait
- Wide-based gait
- Head nod
- Intention tremor
- White matter changes on brain imaging
- Delayed myelination
- Thinning of the optic nerves
- Prominent optic sheaths
Behavioral Psychiatric Manifestations
- Hand flapping
- Hand twirling
MISCELLANEOUS
- Onset in infancy
- One Maltese family has been reported (last curated May 2023)
MOLECULAR BASIS
- Caused by mutation in the translocated promoter region gene (TPR, 189940.0001)
▲ 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 AR 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-79 (MRT79) is caused by compound heterozygous mutation in the TPR gene (189940) on chromosome 1q31. One such family has been reported.

▼ Description

Autosomal recessive intellectual developmental disorder-79 (MRT79) is characterized by global developmental delay apparent from infancy. Affected individuals have mildly delayed walking with an ataxic gait and severely impaired intellectual development with poor or absent speech. Additional features may include postnatal microcephaly and dysmorphic features (Van Bergen et al., 2022).


▼ Clinical Features

Van Bergen et al. (2022) reported 2 sibs, born of unrelated Maltese parents, with severely impaired intellectual development. The sister and brother, aged 21 and 16 years, respectively, showed global developmental delay from infancy, with walking between 25 and 27 months of age and severe language delay with absent speech beyond vocalization or a few words. The sister had mild hypotonia in the neonatal period and experienced episodes of stiffening and jerky movements in the first year of life; EEG was normal. Both sibs showed postnatal microcephaly, with head circumference falling below the first percentile. The patients were dependent for tasks of daily living. Physical examination showed an ataxic wide-based gait, dry eczematous skin, and dysmorphic features, including deep-set eyes, pseudostrabismus, prominent and broad nasal bridge, bulbous nasal tip, thin upper vermilion border, long and thin fingers, fifth finger clinodactyly, and hyperextensible joints. The sister showed head nod, intention tremor, and hand-flapping behaviors, and the brother had hand twirling. Brain imaging in the sister showed nonprogressive white matter changes and delayed myelination, whereas imaging in the brother showed prominent optic sheaths and thinning of the optic nerves.


▼ Inheritance

The transmission pattern of MRT79 in the family reported by Van Bergen et al. (2022) was consistent with autosomal recessive inheritance.


▼ Molecular Genetics

In 2 sibs, born of unrelated Maltese parents, with MRT79, Van Bergen et al. (2022) identified compound heterozygous mutations in the TPR gene: a nonsense mutation (R2209X; 189940.0001) and a splice site mutation (189940.0002). The mutations, which were found by whole-genome sequencing, were each inherited from the unaffected parents; both mutations were absent from the gnomAD database. The findings were consistent with a loss-of-function effect, but the authors suggested that some residual function conferred by the splice site mutation may still exist. Patient fibroblasts showed decreased expression of the TPR protein and decreased density of TPR-containing nuclear pores in the nuclear envelope. The total intensity of mRNA in the nucleus was significantly reduced compared to controls, although cytoplasmic mRNA levels were unchanged. The findings suggested that depletion of TPR may cause defects in transcription with downstream effects on mRNA export.


▼ REFERENCES

  1. Van Bergen, N. J., Bell, K. M., Carey, K., Gear, R., Massey, S., Murrell, E. K., Gallacher, L., Pope, K., Lockhart, P. J., Kornberg, A., Pais, L., Walkiewicz, M., Simons, C., MCRI Rare Diseases Flagship, Wickramasinghe, V. O., White, S. M., Christodoulou, J. Pathogenic variants in nucleoporin TPR (translocated promoter region, nuclear basket protein) cause severe intellectual disability in humans. Hum. Molec. Genet. 31: 362-375, 2022. [PubMed: 34494102, images, related citations] [Full Text]


Creation Date:
Cassandra L. Kniffin : 05/23/2023
Edit History:
carol : 05/30/2023
carol : 05/26/2023
ckniffin : 05/23/2023

# 620393

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 79; MRT79


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number 		Inheritance Phenotype
mapping key 		Gene/Locus Gene/Locus
MIM number
1q31.1 ?Intellectual developmental disorder, autosomal recessive 79 620393 Autosomal recessive 3 TPR 189940

TEXT

A number sign (#) is used with this entry because of evidence that autosomal recessive intellectual developmental disorder-79 (MRT79) is caused by compound heterozygous mutation in the TPR gene (189940) on chromosome 1q31. One such family has been reported.

Description

Autosomal recessive intellectual developmental disorder-79 (MRT79) is characterized by global developmental delay apparent from infancy. Affected individuals have mildly delayed walking with an ataxic gait and severely impaired intellectual development with poor or absent speech. Additional features may include postnatal microcephaly and dysmorphic features (Van Bergen et al., 2022).


Clinical Features

Van Bergen et al. (2022) reported 2 sibs, born of unrelated Maltese parents, with severely impaired intellectual development. The sister and brother, aged 21 and 16 years, respectively, showed global developmental delay from infancy, with walking between 25 and 27 months of age and severe language delay with absent speech beyond vocalization or a few words. The sister had mild hypotonia in the neonatal period and experienced episodes of stiffening and jerky movements in the first year of life; EEG was normal. Both sibs showed postnatal microcephaly, with head circumference falling below the first percentile. The patients were dependent for tasks of daily living. Physical examination showed an ataxic wide-based gait, dry eczematous skin, and dysmorphic features, including deep-set eyes, pseudostrabismus, prominent and broad nasal bridge, bulbous nasal tip, thin upper vermilion border, long and thin fingers, fifth finger clinodactyly, and hyperextensible joints. The sister showed head nod, intention tremor, and hand-flapping behaviors, and the brother had hand twirling. Brain imaging in the sister showed nonprogressive white matter changes and delayed myelination, whereas imaging in the brother showed prominent optic sheaths and thinning of the optic nerves.


Inheritance

The transmission pattern of MRT79 in the family reported by Van Bergen et al. (2022) was consistent with autosomal recessive inheritance.


Molecular Genetics

In 2 sibs, born of unrelated Maltese parents, with MRT79, Van Bergen et al. (2022) identified compound heterozygous mutations in the TPR gene: a nonsense mutation (R2209X; 189940.0001) and a splice site mutation (189940.0002). The mutations, which were found by whole-genome sequencing, were each inherited from the unaffected parents; both mutations were absent from the gnomAD database. The findings were consistent with a loss-of-function effect, but the authors suggested that some residual function conferred by the splice site mutation may still exist. Patient fibroblasts showed decreased expression of the TPR protein and decreased density of TPR-containing nuclear pores in the nuclear envelope. The total intensity of mRNA in the nucleus was significantly reduced compared to controls, although cytoplasmic mRNA levels were unchanged. The findings suggested that depletion of TPR may cause defects in transcription with downstream effects on mRNA export.


REFERENCES

  1. Van Bergen, N. J., Bell, K. M., Carey, K., Gear, R., Massey, S., Murrell, E. K., Gallacher, L., Pope, K., Lockhart, P. J., Kornberg, A., Pais, L., Walkiewicz, M., Simons, C., MCRI Rare Diseases Flagship, Wickramasinghe, V. O., White, S. M., Christodoulou, J. Pathogenic variants in nucleoporin TPR (translocated promoter region, nuclear basket protein) cause severe intellectual disability in humans. Hum. Molec. Genet. 31: 362-375, 2022. [PubMed: 34494102] [Full Text: https://doi.org/10.1093/hmg/ddab248]


Creation Date:
Cassandra L. Kniffin : 05/23/2023

Edit History:
carol : 05/30/2023
carol : 05/26/2023
ckniffin : 05/23/2023



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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: May 14, 2024