PMID: 17574030

Gene: BBS7

HGNC: 18758

Disease: Bardet-Biedl syndrome 7

MONDO: 0014435

InheritancePattern: autosomal recessive

Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).

Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.

ExperimentName: BBS7 interacts with other components of the BBSome.

InteractingGene: BBS4 (HGNC:969)

InteractionType: Physical

InteractionMethod: co-immunoprecipitation

InteractionEvidence: Antibody-based isolation of BBS4 results in co-purification of BBS7, as well as BBS1, BBS2, BBS5, BBS8, and BBS9 in stoichiometric quantities. The co-purifying proteins are shown separated by gel electrophoresis in Figure 1F and were identified and quantified by mass spectrometry in Table S1. All 8 proteins are encoded by genes linked to Bardet-Biedl syndrome.

Case#: Solmaz_2015_Proband_9, male, age 19 years at time of report, part of cohort from Turkey

CasePresentingHPOs: HP:0031418 (Increased body mass index), HP:0000510 (Rod-cone dystrophy), HP:0000750 (Delayed speech and language development), HP:0000218 (High palate), HP:0000678 IDental crowding), HP:0010442 (Polydactyly), HP:0001159 (Syndactyly), HP:0001156 (Brachydactyly), HP:0000026 (Male hypogonadism), HP:0001256 (Intellectual disability, mild)

CaseHPOFreeText: The patient has been diagnosed with Bardet-Biedl syndrome.

CaseNotHPOs: HP:0000365 (Hearing impairment), HP:0000077 (Abnormality of the kidney)

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotyping consisted of an NGS-based panel focusing on the BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, TRIM32, BBS12, MKS1, CEP290, WDPCP, SDCCAG8, NPHP1 loci.

CaseMethod1: NGS-based panel focusing on the BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, TRIM32, BBS12, MKS1, CEP290, WDPCP, SDCCAG8, NPHP1 loci.

CaseMethod2: Sanger sequencing of the BBS7 locus

CaseGenotypingMethod: Genotyping consisted of an NGS-based panel focusing on the BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, TRIM32, BBS12, MKS1, CEP290, WDPCP, SDCCAG8, NPHP1 loci, followed by Sanger sequencing of the BBS7 locus.

Variant: The patient harbors the NM_018190.4:c.712_715del (p.Arg238GlufsTer59) variant in the homozygous state.

CAID: CA3064432

gnomAD: The NM_018190.4:c.712_715del (p.Arg238GlufsTer59) variant is found in gnomAD v2.1.1 at a maximum allele frequency of 0.0001146 (13/113390) in the European non-Finnish population, with 0 homozygotes https://gnomad.broadinstitute.org/variant/4-122775861-CCTCT-C

VariantEvidence: NM_018190.4:c.712_715del (p.Arg238GlufsTer59) is an out-of-frame deletion variant in exon 7 of 18 and is predicted to trigger nonsense-mediated decay or to at least truncate the C-terminal 65% of the protein product.

CaseAddInfo: Consanguinity of this specific patient's family is unknown, but the cohort was reported to have a high rate of consanguineous probands.

CasePMIDs: N/A

PMID: 26518167

Gene: BBS7

HGNC: 18758

Disease: Bardet-Biedl syndrome 7

MONDO: 0014435

InheritancePattern: autosomal recessive

Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).

Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.

Case#: Shen_2019_Patient_III-10, female, age 39 years at time of report, national origin reported as Chinese, ethnicity reported as Miao

CasePresentingHPOs: HP:0001513 (Obesity), HP:0000822 (Hypertension), HP:0000107 (Renal cyst), HP:0010442 (Polydactyly), HP:0000750 (Delayed speech and language development), HP:0000678 (Dental crowding), HP:0011342 (Mild global developmental delay), HP:0001156 (Brachydactyly), HP:0000470 (Short neck), HP:0005280 (Depressed nasal bridge), HP:0000140 (Abnormality of the menstrual cycle)

CaseHPOFreeText: The patient has been diagnosed with Bardet-Biedl syndrome.

CaseNotHPOs: HP:0000134 (Female hypogonadism), HP:0002194 (Delayed gross motor development), HP:0000708 (Atypical behavior), HP:0000819 (Diabetes mellitus), HP:0000365 (Hearing impairment), HP:0000518 (Cataract), HP:0000639 (Nystagmus)

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotyping consisted of exome sequencing.

CaseMethod1: exome sequencing

CaseMethod2: Sanger sequencing of the BBS7 locus

CaseGenotypingMethod: Genotyping consisted of exome sequencing, followed by Sanger sequencing of the BBS7 locus.

Variant: The patient harbors the NM_176824.3(BBS7):c.389_390del (p.Asn130fs) variant in the homozygous state.

ClinVar ID: 216138

gnomAD: The NM_176824.3(BBS7):c.389_390del (p.Asn130fs) variant was not found in gnomAD v2.1.1.

VariantEvidence: NM_176824.3(BBS7):c.389_390del (p.Asn130fs) is an out-of-frame deletion variant in exon 5 of 18 that is predicted to trigger nonsense-mediated decay or at least truncation of the C-terminal 82% of the protein product.

CaseAddInfo: Consanguinity in the proband's family is suspected but has not been confirmed. She has two similarly affected cousins who share the same homozygous genotype. The carrier status of her unaffected parents and an unaffected sibling have been confirmed by genotyping.

CasePMIDs: N/A

PMID: 30839500

Gene: BBS7

HGNC: 18758

Disease: Bardet-Biedl syndrome 7

MONDO: 0014435

InheritancePattern: autosomal recessive

Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).

Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.

ExperimentName: Genetically engineered Bbs7 homozygous knockout mouse

NonHumanModel: Mus musculus

GeneAlteration: The model animals harbor a homozygous replacement of Bbs7 exon 5 with a neomycin cassette, resulting in a frameshifted allele confirmed by western blotting to result in a null effect on the gene product.

ModelPhenotype: HP:0000546 (Retinal degeneration), HP:0032558 (Absent sperm flagella), HP:0001513 (Obesity), HP:0002119 (Ventriculomegaly), HP:0003251 (Male infertility), HP:0030609 (Photoreceptor layer loss on macular OCT), HP:0012258 (Abnormal axonemal organization of respiratory motile cilia), HP:0033524 (Abnormal sperm axoneme morphology)

HumanPhenotype: HP:0001956 (Truncal obesity), HP:0000618 (Blindness), HP:0001249 (Intellectual disability), HP:0001631 (Atrial septal defect), HP:0001640 (Cardiomegaly), HP:0100598 (Pulmonary edema), HP:0012584 (Bilateral renal hypoplasia), HP:0004719 (Hyperechogenic kidneys), HP:0003774 (Stage 5 chronic kidney disease), HP:0000580 (Pigmentary retinopathy), HP:0000648 (Optic atrophy), HP:0008043 (Retinal arteriolar constriction), HP:0007737 (Bone spicule pigmentation of the retina), HP:0007754 (Macular dystrophy)

ModelEvidence: This is a genetically engineered mouse model of biallelic Bbs7 disruption. The mutant animals with biallelic Bbs7 disrupion exhibit photoreceptor inner and outer segment loss (Figure 1), ventriculomegaly (Figure 1), reduced number of cilia and shortened cilia in brain tissue (Figure 2), abnormal axonemal structure / microtubule number abnormality in brain cilia (Figures 2F, 2G), lack of sperm flagella (Figure 3), Abnormal sperm axoneme microtubule organization (Figure 3), destabilization /absence of BBS2 in testes (Figure 4), and abnormal accumulation of some ciliary membrane proteins (dopamine D1 receptor, Figure 6) but not others (polycystin-1 or polycystin-2, Figure 5). Kidney cysts and polydactyly were looked for and found to be absent.

ModelVariant: This model did not introduce a disease-associated variant known from an affected human patient, but rather studied a genetically engineered null variant disrupting Bbs7 expression.

PMID: 23572516

Gene: BBS7

HGNC: 18758

Disease: Bardet-Biedl syndrome 7

MONDO: 0014435

InheritancePattern: autosomal recessive

Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).

Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.

PMID: 25553308

Gene: BBS7

HGNC: 18758

Disease: Bardet-Biedl syndrome 7

MONDO: 0014435

InheritancePattern: autosomal recessive

Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).

Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.

Case#: Shin_2015_Proband, male, age 26 years at time of report, national origin reported as Korean

CasePresentingHPOs: HP:0001956 (Truncal obesity), HP:0000618 (Blindness), HP:0001249 (Intellectual disability), HP:0001631 (Atrial septal defect), HP:0001640 (Cardiomegaly), HP:0100598 (Pulmonary edema), HP:0012584 (Bilateral renal hypoplasia), HP:0004719 (Hyperechogenic kidneys), HP:0003774 (Stage 5 chronic kidney disease), HP:0000580 (Pigmentary retinopathy), HP:0000648 (Optic atrophy), HP:0008043 (Retinal arteriolar constriction), HP:0007737 (Bone spicule pigmentation of the retina), HP:0007754 (Macular dystrophy)

CaseHPOFreeText: The patient has been diagnosed with Bardet-Biedl syndrome and has poor corticomedullary differentiation in the kidneys and optic disc atrophy.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotyping consisted of Sanger sequencing of the BBS1, BBS2, BBS3, BBS4, BBS5, BBS6, BBS8, BBS9, BBS10, BBS11, BBS12, BBS13, and BBS14 genes.

CaseMethod1: Sanger sequencing of the BBS1, BBS2, BBS3, BBS4, BBS5, BBS6, BBS8, BBS9, BBS10, BBS11, BBS12, BBS13, and BBS14 genes

CaseMethod2: Sanger sequencing of the BBS7 locus

CaseGenotypingMethod: Genotyping was performed using Sanger sequencing of the BBS1, BBS2, BBS3, BBS4, BBS5, BBS6, BBS7, BBS8, BBS9, BBS10, BBS11, BBS12, BBS13, and BBS14 genes.

Variant: The patient harbors the NM_018190.4:c.103-1G>A and NM_018190.4:c.728G>A (p.Cys243Tyr) variants in the compound heterozygous state.

ClinVar ID: 166738

CAID: CA358045281

gnomAD: The NM_018190.4:c.103-1G>A variant was not found in gnomAD v2.1.1. The NM_018190.4:c.728G>A (p.Cys243Tyr) variant is found in gnomAD v2.1.1 at a maximum allele frequency of 0.0005515 (11/19944) in the East Asian population, with no homozygotes https://gnomad.broadinstitute.org/variant/4-122774232-C-T

VariantEvidence: NM_018190.4:c.103-1G>A is a canonical splice site variant in intron 2 adjacent to the boundary with exon 3 and does not have functional evidence of an impact on the protein product. NM_018190.4:c.728G>A (p.Cys243Tyr) is a missense variant in exon 8 that does not have functional evidence of an impact on the protein product, but has been previously reported in the homozygous state in a patient affected with retinitis pigmentosa (PMID: 23847139).

CaseAddInfo: Consanguinity is not present in the proband's family. He has a similarly affected brother who shares the same compound heterozygous genotype, and unaffected parents and sibling who each carry one BBS7 variant.

CasePMIDs: N/A

PMID: 12567324

Gene: BBS7

HGNC: 18758

Disease: Bardet-Biedl syndrome 7

MONDO: 0014435

InheritancePattern: autosomal recessive

Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).

Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.

Case#: Badano_2003_Family_KK26_Proband_05, gender, age, and origin not reported.

CasePresentingHPOs: N/A

CaseHPOFreeText: The patient has been diagnosed with Bardet-Biedl syndrome. Specific phenotypes have not been described in detail.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotyping consisted of linkage mapping using a 10-cM linkage map set to identify regions of homozygosity unique to the affected family member only.

CaseMethod1: Homozygosity analysis

CaseMethod2: Sanger sequencing of the BBS7 locus

CaseGenotypingMethod: Genotyping first identify regions of homozygosity unique to the affected family member, then performed Sanger sequencing of the BBS7 locus.

Variant: The patient harbors the NM_176824.3(BBS7):c.709_712del (p.Lys237fs) variant in the homozygous state.

ClinVar ID: 3017

gnomAD: The NM_176824.3(BBS7):c.709_712del (p.Lys237fs) variant was not found in gnomAD v2.1.1.

VariantEvidence: NM_176824.3(BBS7):c.709_712del (p.Lys237fs) is an out-of-frame deletion variant in exon 7 of 18 and is predicted to trigger nonsense-mediated decay or to at least truncate the C-terminal 67% of the protein product.

CaseAddInfo: The proband is a member of family KK26, which is known to be consanguineous. The proband has two unaffected carrier parents, 5 unaffected carrier siblings, and 1 unaffected non-carrier sibling.

CasePMIDs: N/A

ExperimentName: Naturally occurring bbs-7 loss-of-function C. elegans model

NonHumanModel: C. elegans

GeneAlteration: The model animals harbor a naturally occurring homozygous nonsense variant at nucleotide 2899 within the bbs-7 locus.

ModelPhenotype: short cilia, defective chemotaxis, defective intraflagellar transport, IFT mislocalization

HumanPhenotype: HP:0001956 (Truncal obesity), HP:0000618 (Blindness), HP:0001249 (Intellectual disability), HP:0001631 (Atrial septal defect), HP:0001640 (Cardiomegaly), HP:0100598 (Pulmonary edema), HP:0012584 (Bilateral renal hypoplasia), HP:0004719 (Hyperechogenic kidneys), HP:0003774 (Stage 5 chronic kidney disease), HP:0000580 (Pigmentary retinopathy), HP:0000648 (Optic atrophy), HP:0008043 (Retinal arteriolar constriction), HP:0007737 (Bone spicule pigmentation of the retina), HP:0007754 (Macular dystrophy)

ModelEvidence: This is a naturally occurring C. elegans model of biallelic bbs-7 disruption. The mutant animals exhibit reduced chemotaxis (dependent on two chemosensory neurons, Figure 2E), shorter cilia (Figure 3), defective localization of IFT particles (Figure 4), and reduced intraflagellar transport (Figure 5). Rescue of chemotaxis with expression of the wild-type C. elegans bbs-7 gene directly linked the defect with bbs-7 (Figure 2E).

ModelVariant: This model did not introduce a disease-associated variant known from an affected human patient, but rather studied a naturally occurring and apparent null variant disrupting bbs-7 expression.

PMID: 15231740

Gene: BBS7

HGNC: 18758

Disease: Bardet-Biedl syndrome 7

MONDO: 0014435

InheritancePattern: autosomal recessive

Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).

Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.

Case#: Fattahi_2014_Patient_40302, male, age not specified, ethnicity reported as Fars, national origin reported as Iranian

CasePresentingHPOs: HP:0001513 (Obesity), HP:0000510 (Rod-cone dystrophy), HP:0000545 (Myopia), HP:0001161 (Hand polydactyly), HP:0001829 (Foot polydactyly), HP:0000077 (Abnormality of the kidney), HP:0000026 (Male hypogonadism), HP:0002463 (Language impairment), HP:0000639 (Nystagmus), HP:0001627 (Abnormal heart morphology), HP:0000708 (Atypical behavior), HP:0002251 (Aganglionic megacolon), HP:0001156 (Brachydactyly), HP:0001511 (Intrauterine growth retardation)

CaseHPOFreeText: The patient has been diagnosed with Bardet-Biedl syndrome and retinitis pigmentosa.

CaseNotHPOs: HP:0000518 (Cataract), HP:0000662 (Nyctalopia), HP:0000486 (Strabismus), HP:0001328 (Specific learning disability)

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotyping consisted of Sanger sequencing of the BBS1, BBS2, BBS10, BBS3, BBS4, BBS6, BBS9, and BBS12 genes.

CaseMethod1: Sanger sequencing of the BBS1, BBS2, BBS10, BBS3, BBS4, BBS6, BBS9, and BBS12 loci

CaseMethod2: Sanger sequencing of the BBS7 locus.

CaseGenotypingMethod: Genotyping was performed using Sanger sequencing of the BSB1, BBS2, BBS10, BBS3, BBS4, BBS6, BBS7, BBS9, and BBS12 genes.

Variant: The patient harbors the NM_018190.4:c.1342_1346del (p.Gln448Argfs*13) and NM_018190.4:c.1443T>A (p.Cys481Ter) variants in the compound heterozygous state.

CAID: CA2580617740, CA358058685

gnomAD: The NM_018190.4:c.1342_1346del (p.Gln448Argfs*13) and NM_018190.4:c.1443T>A (p.Cys481Ter) variants were not found in gnomAD v2.1.1.

VariantEvidence: NM_018190.4:c.1342_1346del (p.Gln448Argfs*13) is a frameshift variant in exon 13 of 18 that is predicted to trigger nonsense-mediated decay or to at least truncate the C-terminal 37% of the protein product. NM_018190.4:c.1443T>A (p.Cys481Ter) is a nonsense variant in exon 14 of 18 that is predicted to trigger nonsense-mediated decay or to at least truncate the C-terminal 33% of the protein product..

CaseAddInfo: Consanguinity is not present in the proband's family.

CasePMIDs: N/A

Case#: Suspitsin_2015_Proband_II.4, male, age 7 years at time of report, national origin reported as Russian

CasePresentingHPOs: HP:0004324 (Increased body weight), HP:0012743 (Abdominal obesity), HP:0000510 (Rod-cone dystrophy), HP:0100259 (Postaxial polydactyly), HP:0011220 (Prominent forehead), HP:0005280 (Depressed nasal bridge), HP:0000054 (Micropenis), HP:0001256 (Intellectual disability, mild), HP:5200120 (Abnormality in emotional social interactions)

CaseHPOFreeText: The patient has been diagnosed with Bardet-Biedl syndrome and retinitis pigmentosa.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotyping consisted of exome sequencing, focused on the BBS1-BBS19 loci.

CaseMethod1: exome sequencing

CaseMethod2: N/A

CaseGenotypingMethod: Genotyping consisted of exome sequencing, focused on the BBS1-BBS19 loci.

Variant: The patient harbors the NM_176824.3(BBS7):c.1967_1968delinsC (p.Leu656fs) variant in the homozygous state.

ClinVar ID: 162088

gnomAD: The NM_176824.3(BBS7):c.1967_1968delinsC (p.Leu656fs) variant was not found in gnomAD v2.1.1. However, the authors note that the healthy blood donors from the Russian population do carry the allele in the heterozygous state at a low frequency (0.07%).

VariantEvidence: NM_176824.3(BBS7):c.1967_1968delinsC (p.Leu656fs) is an out-of-frame indel in exon 18 of 18 and is not predicted to trigger nonsense-mediated decay but rather to truncate the C-terminal 8% of the protein product.

CaseAddInfo: The proband is a member of a non-consanguineous family, and has two unaffected carrier parents, an unaffected carrier sibling, and a similarly affected sister sharing the same homozygous genotype.

CasePMIDs: N/A

PMID: 26557828

Gene: BBS7

HGNC: 18758

Disease: Bardet-Biedl syndrome 7

MONDO: 0014435

InheritancePattern: autosomal recessive

Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).

Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.

ExperimentName: Naturally occurring BBS7 loss-of-function primate model

NonHumanModel: Rhesus macaque

GeneAlteration: The model animals harbor a naturally occurring homozygous frameshift variant at nucleotide 160 within exon 3 of the BBS7 locus.

ModelPhenotype: HP:0000608 (Macular degeneration), HP:0030609 (Photoreceptor layer loss on macular OCT), HP:0000580 (Pigmentary retinopathy), HP:0008046 (Abnormal retinal vascular morphology), progressive kidney disease, HP:0030483 (Reduced amplitude of dark-adapted bright flash electroretinogram a-wave), HP:0030469 (Abnormal dark-adapted electroretinogram), HP:0008275 (Abnormal light-adapted electroretinogram), HP:0002171 (Gliosis), HP:0000083 (Renal insufficiency), HP:0012210 (Abnormal renal morphology), HP:0002119 (Ventriculomegaly), HP:0008734 (Decreased testicular size)

HumanPhenotype: HP:0001956 (Truncal obesity), HP:0000618 (Blindness), HP:0001249 (Intellectual disability), HP:0001631 (Atrial septal defect), HP:0001640 (Cardiomegaly), HP:0100598 (Pulmonary edema), HP:0012584 (Bilateral renal hypoplasia), HP:0004719 (Hyperechogenic kidneys), HP:0003774 (Stage 5 chronic kidney disease), HP:0000580 (Pigmentary retinopathy), HP:0000648 (Optic atrophy), HP:0008043 (Retinal arteriolar constriction), HP:0007737 (Bone spicule pigmentation of the retina), HP:0007754 (Macular dystrophy)

ModelEvidence: This is a naturally occurring Rhesus macaque model of biallelic BBS7 disruption. The mutant animals exhibit hypoechoic kidney lesions (Figure 1), retinal atrophy with lack of retinal vasculature (Figure 3A), RPE atrophy (Figure 3B), severe atrophy of retinal layers by OCT with greater severity centrally (Figure 3C), retinal gliosis (Figure 3D), Severely reduced amplitudes and delayed time courses of both dark-adapted and light-adapted flicker ERG (Figure 4), reduced brain volume (Figure 5B), dilation of the lateral ventricle (Figure 5A), cystic kidney tubules with loss of nephrons replaced with fibrosis, tubule atrophy, and ectasia (Figure 7), reduced size and histological maturity of testes (Table 1), and vision deficits (Table 1).

ModelVariant: This model did not introduce a disease-associated variant known from an affected human patient, but rather studied a naturally occurring and apparent null variant disrupting BBS7 expression.

PMID: 31589838

Gene: BBS7

HGNC: 18758

Disease: Bardet-Biedl syndrome 7

MONDO: 0014435

InheritancePattern: autosomal recessive

Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).

Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.

PMID: 19402160

Gene: BBS7

HGNC: 18758

Disease: Bardet-Biedl syndrome 7

MONDO: 0014435

InheritancePattern: autosomal recessive

Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).

Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.

Case#: Bin_2009_Family_04-01_Case_26, female, age 11.6 years at time of report, national origin reported as from Peru

CasePresentingHPOs: HP:0001513 (Obesity), HP:0010442 (Polydactyly), HP:0100543 (Cognitive impairment), HP:0012758 (Neurodevelopmental delay), HP:0003077 (Hyperlipidemia), HP:0034685 (Abnormal liver enzyme activity or concentration), HP:0000077 (Abnormality of the kidney), HP:0410042 (Abnormal liver morphology), HP:0030515 (Moderately reduced visual acuity), HP:0000548 (Cone/cone-rod dystrophy), HP:0001133 (Constriction of peripheral visual field)

CaseHPOFreeText: The patient has been diagnosed with Bardet-Biedl syndrome.

CaseNotHPOs: HP:0000639 (Nystagmus), HP:0000518 (Cataract)

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotyping consisted of Sanger sequencing of the TTC8 locus.

CaseMethod1: Sanger sequencing of the TTC8 locus

CaseMethod2: Sanger sequencing of the BBS7 locus

CaseGenotypingMethod: Genotyping consisted of Sanger sequencing of the TTC8 and BBS7 loci.

Variant: The patient harbors the NM_176824.3:c.712_715del (p.Arg238GlufsTer?) and NM_176824.3:c.1121C>G (Ser374Ter) variants in the compound heterozygous state.

CAID: CA3064432, CA358062298

gnomAD: The NM_176824.3:c.1121C>G (Ser374Ter) variant is found in gnomAD v2.1.1 at a maximum allele frequency of 0.0001633 (1/6124 in the Other population), with 0 homozygotes. https://gnomad.broadinstitute.org/variant/4-122766768-G-C The NM_176824.3:c.712_715del (p.Arg238GlufsTer?) variant is found in gnomAD v2.1.1 at a maximum allele frequency of 0.0001146 (13/113390) in the European non-FInnish population), with 0 homozygotes.

VariantEvidence: NM_176824.3:c.1121C>G (Ser374Ter) is a nonsense variant in exon 11 of 18 that is predicted to trigger nonsense-mediated decay or at least truncation of the C-terminal 48% of the protein product. NM_176824.3:c.712_715del (p.Arg238GlufsTer?)is a frameshift variant in exon 7 of 18 that is predicted to trigger nonsense-mediated decay or at least truncation of the C-terminal 67% of the protein product.

CaseAddInfo: Consanguinity in the proband's family has not been reported. The carrier status of her unaffected parents and an unaffected sibling have been confirmed by genotyping.

CasePMIDs: N/A