Meckel Syndrome, Type 10

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).

Clinical Features

Dowdle et al. (2011) reported 2 fetuses with Meckel syndrome who were born in 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.

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.

Molecular Genetics

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.

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.