Entry - #619988 - INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 77; MRT77 - OMIM

 
ICD+
# 619988

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 77; MRT77


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number 		Inheritance Phenotype
mapping key 		Gene/Locus Gene/Locus
MIM number
1p36.32 Intellectual developmental disorder, autosomal recessive 77 619988 AR 3 CEP104 616690
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
NEUROLOGIC
Central Nervous System
- Global developmental delay
- Motor delay
- Delayed walking
- Unsteady gait (in some patients)
- Impaired intellectual development, variable (IQ range from 25 to 55, in some patients)
- Poor or absent speech
- Normal brain imaging
Behavioral Psychiatric Manifestations
- Autistic features (in some patients)
- Stereotypies
- Poor communication
MISCELLANEOUS
- Onset in infancy
- Three unrelated consanguineous Iranian families have been reported (last curated August 2022)
MOLECULAR BASIS
- Caused by mutation in the centrosomal protein, 1040-kD gene (CEP104, 616690.0005)
▲ Close
Intellectual developmental disorder, autosomal recessive - PS249500 - 71 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 AR 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
12q14.2 Intellectual developmental disorder, autosomal recessive 83 AR 3 621100 KICS2 617420
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-77 (MRT77) is caused by homozygous mutation in the CEP104 gene (616690) on chromosome 1p36.

▼ Description

Autosomal recessive intellectual developmental disorder-77 (MRT77) is a nonsyndromic neurodevelopmental disorder characterized by global developmental delay with variably impaired cognitive development apparent from infancy. Affected individuals usually have delayed walking, sometimes with an unsteady gait, and may have poor speech and communication. Brain imaging is normal, and there are no additional significant neurologic abnormalities (Khoshbakht et al., 2021).

Mutation in the CEP104 gene also causes a form of Joubert syndrome (JBTS25; 616781).

▼ Clinical Features

Khoshbakht et al. (2021) reported 4 patients, including 3 sibs, from 2 unrelated consanguineous Iranian families with an intellectual developmental disorder. A 10-year-old boy (family 8800138) showed global developmental delay with delayed walking and severely impaired intellectual development (IQ of 25) with speech and communication problems. Other minor features included joint laxity, poor wound healing, and autistic features with stereotypies and hand-biting behavior. Overall growth and brain imaging were normal. Three sibs (family 9100012) who were 20 to 30 years of age had a history of global developmental delay with walking by age 3 years and saying single words around age 4. As young adults, their gait was normal and they could speak in multiword phrases; IQ ranged from 50 to 55. Brain imaging, performed in 1 sib, was normal, thus distinguishing the phenotype from Joubert syndrome.

Badv et al. (2022) reported a 7.5-year-old girl, born of consanguineous Iranian parents, with global developmental delay apparent from infancy. She demonstrated transient head tremors and nystagmus as an infant that resolved by 1 year of age. She walked with an unsteady gait around 18 months of age and showed impaired intellectual development with social communication problems; nasal speech was noted. Brain imaging was normal.


▼ Inheritance

The transmission pattern of MRT77 in the families reported by Khoshbakht et al. (2021) was consistent with autosomal recessive inheritance.


▼ Molecular Genetics

In 4 patients from 2 unrelated consanguineous Iranian families (families 8800138 and 9100012), with MRT77, Khoshbakht et al. (2021) identified homozygous frameshift mutations in the CEP104 gene (616690.0005 and 616690.0006). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Neither was present in the ClinVar, 1000 Genomes Project, or ExAC databases. Patient-derived lymphoblastoid cells showed a significant reduction in CEP104 transcripts, and Western blot analysis was consistent with low expression of a truncated protein, suggesting incomplete nonsense-mediated mRNA decay. Additional functional studies were not performed.

In a 7.5-year-old girl, born of consanguineous Iranian parents, with MRT77, Badv et al. (2022) identified a homozygous nonsense mutation in the CEP104 gene (R215X; 616690.0007). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. It was not reported in the 1000 Genomes Project database. Functional studies of the variant and studies of patient cells were not performed.


▼ REFERENCES

  1. Badv, R. S., Mahdiannasser, M., Rasoulinezhad, M., Habibi, L., Rashidi-Nezhad, A. CEP104 gene may involve in the pathogenesis of a new developmental disorder other than joubert (sic) syndrome. Molec. Biol. Rep. 49: 7231-7237, 2022. [PubMed: 35359234, related citations] [Full Text]

  2. Khoshbakht, S., Beheshtian, M., Fattahi, Z., Bazazzadegan, N., Parsimehr, E., Fadaee, M., Vazehan, R., Faraji Zonooz, M., Abolhassani, A., Makvand, M., Kariminejad, A., Celik, A., Kahrizi, K., Najmabadi, H. CEP104 and CEP290; genes with ciliary functions cause intellectual disability in multiple families. Arch. Iran. Med. 24: 364-373, 2021. [PubMed: 34196201, related citations] [Full Text]


Creation Date:
Cassandra L. Kniffin : 08/08/2022
Edit History:
alopez : 08/09/2022
alopez : 08/09/2022
ckniffin : 08/08/2022

# 619988

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 77; MRT77


ORPHA: 88616;   DO: 0081236;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number 		Inheritance Phenotype
mapping key 		Gene/Locus Gene/Locus
MIM number
1p36.32 Intellectual developmental disorder, autosomal recessive 77 619988 Autosomal recessive 3 CEP104 616690

TEXT

A number sign (#) is used with this entry because of evidence that autosomal recessive intellectual developmental disorder-77 (MRT77) is caused by homozygous mutation in the CEP104 gene (616690) on chromosome 1p36.

Description

Autosomal recessive intellectual developmental disorder-77 (MRT77) is a nonsyndromic neurodevelopmental disorder characterized by global developmental delay with variably impaired cognitive development apparent from infancy. Affected individuals usually have delayed walking, sometimes with an unsteady gait, and may have poor speech and communication. Brain imaging is normal, and there are no additional significant neurologic abnormalities (Khoshbakht et al., 2021).

Mutation in the CEP104 gene also causes a form of Joubert syndrome (JBTS25; 616781).

Clinical Features

Khoshbakht et al. (2021) reported 4 patients, including 3 sibs, from 2 unrelated consanguineous Iranian families with an intellectual developmental disorder. A 10-year-old boy (family 8800138) showed global developmental delay with delayed walking and severely impaired intellectual development (IQ of 25) with speech and communication problems. Other minor features included joint laxity, poor wound healing, and autistic features with stereotypies and hand-biting behavior. Overall growth and brain imaging were normal. Three sibs (family 9100012) who were 20 to 30 years of age had a history of global developmental delay with walking by age 3 years and saying single words around age 4. As young adults, their gait was normal and they could speak in multiword phrases; IQ ranged from 50 to 55. Brain imaging, performed in 1 sib, was normal, thus distinguishing the phenotype from Joubert syndrome.

Badv et al. (2022) reported a 7.5-year-old girl, born of consanguineous Iranian parents, with global developmental delay apparent from infancy. She demonstrated transient head tremors and nystagmus as an infant that resolved by 1 year of age. She walked with an unsteady gait around 18 months of age and showed impaired intellectual development with social communication problems; nasal speech was noted. Brain imaging was normal.


Inheritance

The transmission pattern of MRT77 in the families reported by Khoshbakht et al. (2021) was consistent with autosomal recessive inheritance.


Molecular Genetics

In 4 patients from 2 unrelated consanguineous Iranian families (families 8800138 and 9100012), with MRT77, Khoshbakht et al. (2021) identified homozygous frameshift mutations in the CEP104 gene (616690.0005 and 616690.0006). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Neither was present in the ClinVar, 1000 Genomes Project, or ExAC databases. Patient-derived lymphoblastoid cells showed a significant reduction in CEP104 transcripts, and Western blot analysis was consistent with low expression of a truncated protein, suggesting incomplete nonsense-mediated mRNA decay. Additional functional studies were not performed.

In a 7.5-year-old girl, born of consanguineous Iranian parents, with MRT77, Badv et al. (2022) identified a homozygous nonsense mutation in the CEP104 gene (R215X; 616690.0007). The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family. It was not reported in the 1000 Genomes Project database. Functional studies of the variant and studies of patient cells were not performed.


REFERENCES

  1. Badv, R. S., Mahdiannasser, M., Rasoulinezhad, M., Habibi, L., Rashidi-Nezhad, A. CEP104 gene may involve in the pathogenesis of a new developmental disorder other than joubert (sic) syndrome. Molec. Biol. Rep. 49: 7231-7237, 2022. [PubMed: 35359234] [Full Text: https://doi.org/10.1007/s11033-022-07353-w]

  2. Khoshbakht, S., Beheshtian, M., Fattahi, Z., Bazazzadegan, N., Parsimehr, E., Fadaee, M., Vazehan, R., Faraji Zonooz, M., Abolhassani, A., Makvand, M., Kariminejad, A., Celik, A., Kahrizi, K., Najmabadi, H. CEP104 and CEP290; genes with ciliary functions cause intellectual disability in multiple families. Arch. Iran. Med. 24: 364-373, 2021. [PubMed: 34196201] [Full Text: https://doi.org/10.34172/aim.2021.53]


Creation Date:
Cassandra L. Kniffin : 08/08/2022

Edit History:
alopez : 08/09/2022
alopez : 08/09/2022
ckniffin : 08/08/2022



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OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2025 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® 1966-2025 Johns Hopkins University.
Printed: March 14, 2025