#614175
Table of Contents
| Location | Phenotype | Inheritance |
Phenotype mapping key |
Phenotype MIM number |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q32.1 | ?Meckel syndrome 12 | AR | 3 | 616258 | KIF14 | 611279 |
| 3q22.1 | Meckel syndrome 7 | AR | 3 | 267010 | NPHP3 | 608002 |
| 4p15.32 | Meckel syndrome 6 | AR | 3 | 612284 | CC2D2A | 612013 |
| 5q31.1 | Meckel syndrome 14 | AR | 3 | 619879 | TXNDC15 | 617778 |
| 8q22.1 | Meckel syndrome 3 | AR | 3 | 607361 | TMEM67 | 609884 |
| 11q12.2 | Meckel syndrome 2 | AR | 3 | 603194 | TMEM216 | 613277 |
| 12q21.32 | Meckel syndrome 4 | AR | 3 | 611134 | CEP290 | 610142 |
| 12q24.31 | ?Meckel syndrome 8 | AR | 3 | 613885 | TCTN2 | 613846 |
| 16q12.2 | Meckel syndrome 5 | AR | 3 | 611561 | RPGRIP1L | 610937 |
| 16q23.1 | Meckel syndrome 11 | AR | 3 | 615397 | TMEM231 | 614949 |
| 17p13.1 | ?Joubert syndrome 29 | AR | 3 | 617562 | TMEM107 | 616183 |
| 17p13.1 | Meckel syndrome 13 | AR | 3 | 617562 | TMEM107 | 616183 |
| 17p11.2 | ?Meckel syndrome 9 | AR | 3 | 614209 | B9D1 | 614144 |
| 17q22 | Meckel syndrome 1 | AR | 3 | 249000 | MKS1 | 609883 |
| 19q13.2 | Joubert syndrome 34 | AR | 3 | 614175 | B9D2 | 611951 |
| 19q13.2 | ?Meckel syndrome 10 | AR | 3 | 614175 | B9D2 | 611951 |
A number sign (#) is used with this entry because of evidence that Meckel syndrome type 10 (MKS10) and Joubert syndrome-34 (JBTS34) are caused by homozygous or compound heterozygous mutation in the B9D2 gene (611951) on chromosome 19q13.
For a general phenotypic description and a discussion of genetic heterogeneity of Meckel syndrome, see MKS1 (249000); for similar discussions regarding Joubert syndrome, see JBTS1 (213300).
Meckel Syndrome 10
Dowdle et al. (2011) reported 2 fetuses with Meckel syndrome and mutation in the B9D2 gene who were born into a consanguineous family from Surinam with an Indian-Pakistani background. They were terminated at 17 and 29 weeks' gestation, respectively. Clinical features included occipital encephalocele, postaxial polydactyly of the hands and feet, renal cysts, and hepatic ductal plate malformations; 1 fetus had anencephaly.
Radhakrishnan et al. (2019) reported an Indian fetus with Meckel syndrome diagnosed on antenatal ultrasonography, and mutation in the B9D2 gene. Autopsy revealed inferior vermian agenesis, cerebellar hypoplasia, dilated fourth ventricle, bifid uvula, polydactyly of the right hand and left foot, bilateral ulnar deviation and camptodactyly of the hands, bent long bones, and microphallus with hypospadias. Kidneys were normal, with unremarkable histopathology.
Joubert Syndrome 34
Bachmann-Gagescu et al. (2015) described 2 unrelated patients with Joubert syndrome and mutation in the B9D2 gene. Both patients had the molar tooth sign, polydactyly, and seizures. Patient UW284-3 had cleft palate, tibial and fibular mesomelic dysplasia, shunted hydrocephalus, interpeduncular heterotopia, poor pupillary response to light, micropenis, hearing loss, and patent ductus arteriosus. Patient UW309-3 had abnormal EEG, hypospadias, and dysmorphic features including frontal bossing, epicanthus, dysplastic ears, down-turned corners of the mouth, retrognathia, ptosis, and right eye exotropia.
Meckel Syndrome 10
In 2 fetuses with MKS10, Dowdle et al. (2011) identified a homozygous mutation in the B9D2 gene (S101R; 611951.0001). The proband was from a larger cohort of 96 unrelated MKS patients. Immunoprecipitation studies showed that the mutant S101R protein failed to interact with MKS1 (609883), although it retained its ability to interact with B9D1 (614144). The results indicated that a complex of B9 proteins cooperate to support mammalian ciliogenesis and ciliary protein localization. Disruption of any of the members of this complex can result in Meckel syndrome.
By whole-exome sequencing in an Indian fetus with Meckel syndrome, Radhakrishnan et al. (2019) identified homozygosity for a missense mutation in the B9D2 gene (H5Q; 611951.0005). The mutation segregated with disease in the family and was not found in the gnomAD database.
Joubert Syndrome 34
In 2 unrelated patients (UW309-3 and UW284-3) with Joubert syndrome, Bachmann-Gagescu et al. (2015) identified homozygous (611951.0002) or compound heterozygous (611951.0003-611951.0004) mutations in the B9D2 gene, respectively. The mutations were identified by sequencing 27 candidate genes in 428 affected individuals from 363 families by molecular inversion probe targeted capture followed by next-generation sequencing. No functional studies of the variants were performed.
Bachmann-Gagescu, R., Dempsey, J. C., Phelps, I. G., O'Roak, B. J., Knutzen, D. M., Rue, T. C., Ishak, G. E., Isabella, C. R., Gorden, N., Adkins, J., Boyle, E. A., de Lacy, N., and 17 others. Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. J. Med. Genet. 52: 514-522, 2015. [PubMed: 26092869, images, related citations] [Full Text]
Dowdle, W. E., Robinson, J. F., Kneist, A., Sirerol-Piquer, M. S., Frints, S. G. M., Corbit, K. C., Zaghloul, N. A., van Lijnschoten, G., Mulders, L., Verver, D. E., Zerres, K., Reed, R. R., Attie-Bitach, T., Johnson, C. A., Garcia-Verdugo, J. M., Katsanis, N., Bergmann, C., Reiter, J. F. Disruption of a ciliary B9 protein complex causes Meckel syndrome. Am. J. Hum. Genet. 89: 94-110, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011. [PubMed: 21763481, images, related citations] [Full Text]
Radhakrishnan, P., Nayak, S. S., Shukla, A., Lindstrand, A., Girisha, K. M. Meckel syndrome: clinical and mutation profile in six fetuses. Clin. Genet. 96: 560-565, 2019. [PubMed: 31411728, related citations] [Full Text]
Other entities represented in this entry:
ORPHA: 564;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19q13.2 | Joubert syndrome 34 | 614175 | Autosomal recessive | 3 | B9D2 | 611951 |
| 19q13.2 | ?Meckel syndrome 10 | 614175 | Autosomal recessive | 3 | B9D2 | 611951 |
A number sign (#) is used with this entry because of evidence that Meckel syndrome type 10 (MKS10) and Joubert syndrome-34 (JBTS34) are caused by homozygous or compound heterozygous mutation in the B9D2 gene (611951) on chromosome 19q13.
For a general phenotypic description and a discussion of genetic heterogeneity of Meckel syndrome, see MKS1 (249000); for similar discussions regarding Joubert syndrome, see JBTS1 (213300).
Meckel Syndrome 10
Dowdle et al. (2011) reported 2 fetuses with Meckel syndrome and mutation in the B9D2 gene who were born into a consanguineous family from Surinam with an Indian-Pakistani background. They were terminated at 17 and 29 weeks' gestation, respectively. Clinical features included occipital encephalocele, postaxial polydactyly of the hands and feet, renal cysts, and hepatic ductal plate malformations; 1 fetus had anencephaly.
Radhakrishnan et al. (2019) reported an Indian fetus with Meckel syndrome diagnosed on antenatal ultrasonography, and mutation in the B9D2 gene. Autopsy revealed inferior vermian agenesis, cerebellar hypoplasia, dilated fourth ventricle, bifid uvula, polydactyly of the right hand and left foot, bilateral ulnar deviation and camptodactyly of the hands, bent long bones, and microphallus with hypospadias. Kidneys were normal, with unremarkable histopathology.
Joubert Syndrome 34
Bachmann-Gagescu et al. (2015) described 2 unrelated patients with Joubert syndrome and mutation in the B9D2 gene. Both patients had the molar tooth sign, polydactyly, and seizures. Patient UW284-3 had cleft palate, tibial and fibular mesomelic dysplasia, shunted hydrocephalus, interpeduncular heterotopia, poor pupillary response to light, micropenis, hearing loss, and patent ductus arteriosus. Patient UW309-3 had abnormal EEG, hypospadias, and dysmorphic features including frontal bossing, epicanthus, dysplastic ears, down-turned corners of the mouth, retrognathia, ptosis, and right eye exotropia.
Meckel Syndrome 10
In 2 fetuses with MKS10, Dowdle et al. (2011) identified a homozygous mutation in the B9D2 gene (S101R; 611951.0001). The proband was from a larger cohort of 96 unrelated MKS patients. Immunoprecipitation studies showed that the mutant S101R protein failed to interact with MKS1 (609883), although it retained its ability to interact with B9D1 (614144). The results indicated that a complex of B9 proteins cooperate to support mammalian ciliogenesis and ciliary protein localization. Disruption of any of the members of this complex can result in Meckel syndrome.
By whole-exome sequencing in an Indian fetus with Meckel syndrome, Radhakrishnan et al. (2019) identified homozygosity for a missense mutation in the B9D2 gene (H5Q; 611951.0005). The mutation segregated with disease in the family and was not found in the gnomAD database.
Joubert Syndrome 34
In 2 unrelated patients (UW309-3 and UW284-3) with Joubert syndrome, Bachmann-Gagescu et al. (2015) identified homozygous (611951.0002) or compound heterozygous (611951.0003-611951.0004) mutations in the B9D2 gene, respectively. The mutations were identified by sequencing 27 candidate genes in 428 affected individuals from 363 families by molecular inversion probe targeted capture followed by next-generation sequencing. No functional studies of the variants were performed.
Bachmann-Gagescu, R., Dempsey, J. C., Phelps, I. G., O'Roak, B. J., Knutzen, D. M., Rue, T. C., Ishak, G. E., Isabella, C. R., Gorden, N., Adkins, J., Boyle, E. A., de Lacy, N., and 17 others. Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. J. Med. Genet. 52: 514-522, 2015. [PubMed: 26092869] [Full Text: https://doi.org/10.1136/jmedgenet-2015-103087]
Dowdle, W. E., Robinson, J. F., Kneist, A., Sirerol-Piquer, M. S., Frints, S. G. M., Corbit, K. C., Zaghloul, N. A., van Lijnschoten, G., Mulders, L., Verver, D. E., Zerres, K., Reed, R. R., Attie-Bitach, T., Johnson, C. A., Garcia-Verdugo, J. M., Katsanis, N., Bergmann, C., Reiter, J. F. Disruption of a ciliary B9 protein complex causes Meckel syndrome. Am. J. Hum. Genet. 89: 94-110, 2011. Note: Erratum: Am. J. Hum. Genet. 89: 589 only, 2011. [PubMed: 21763481] [Full Text: https://doi.org/10.1016/j.ajhg.2011.06.003]
Radhakrishnan, P., Nayak, S. S., Shukla, A., Lindstrand, A., Girisha, K. M. Meckel syndrome: clinical and mutation profile in six fetuses. Clin. Genet. 96: 560-565, 2019. [PubMed: 31411728] [Full Text: https://doi.org/10.1111/cge.13623]
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