Table 2.
Genotypes and phenotypes of 14 individuals with BBS (12 families) with only one mutated allele detected in a known BBS gene (BBS1–BBS12)
| Family [Individual (alias)] | Cardinal features
|
Secondary signs | Origin | BBS genea | Nucleotide change (zygosity state)b | Amino acid change (segregation) | Count/coverage (% frequency) | Mutation assignmentc | Mutation reference | PolyPhen PSIC score | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Retinitis pigmentosa | Postaxial polydactyly | Obesity | Hypogonadism | Renal anomalies | |||||||||||
| A2499 | Y | Y | N | N | Y | – | ND | 1 | c.734 C>T (h) | p.P245L | 6/382 (1.6%) | All pat seq | Present study | 2.328 | |
| 9 | c.2849 T>A (h) | p.L781Q | 4/425 (0.9%) | CEL I | Present study | 1.885 | |||||||||
| A2517 | Y | Y | N | N | Y | DD, HAP, OB | ND | 1 | c.871 C>T (h) | p.Q291X | 1,607/54,862 (2.9%) | CEL I | Beales et al. 2003 | n/a | |
| AR786 (A2868) | -03 | Y | N | Y | ND | N | MC, MD, MR, SD | N. Eur. | 1 | c.1169 T>G (h) | p.M390R | 2/22 (9.1%) | All pat seq | Mykytyn et al. 2002 | 2.703 |
| -04 | Y | Y | ND | ND | N | MR, SD, SDys | c.1169 T>G (H) | ||||||||
| PB236 (A2010) | -II1 | Y | Y | Y | ND | Y | ATX, BD, STBI | Turkey | 2 | c.1891G>A (h) | p.A631T | 10/494 (2.0%) | All pat seq | Present study | 1.522 |
| AR348 (A2848) | -03 | Y | Y | Y | ND | ND | – | N. Eur. | 4 | c.218A>G (h) | p.Q73R | 74/3,159 (2.3%) | CEL I | Present study | 1.574 |
| AR364 (A2849) | -02 | Y | Y | Y | Y | Y | DD, HNP | N. Eur. | 5 | c.551A>G (h) | p.N184S | 41/1,353 (3.0%) | All pat seq | Li et al. 2004 | 2.211 |
| AR755 (A2867)d | -03 | Y | Y | Y | ND | N | BD, DD, DF, SD | N. Eur. | 5 | c.551A>G (h) | p.N184S | 41/1,353 (3.0%) | All pat seq | Li et al. 2004 | 2.211 |
| A786 | -II1 | N | Y | Y | Y | Y | ASD, MR, MY, Sz | Macedonia | 6 | c.724G>T (h) | p.A242S | 216/12,651 (1.7%) | All pat seq | Stone et al. 2000 | 1.280 |
| AR800 (A2870) | -03 | Y | Y | Y | Y | ND | MR, SS, STBI | N. Eur. | 6 | c.724G>T (h) | p.A242S | 1,878/55,174 (3.4%) | CEL I | Stone et al. 2000 | 1.280 |
| AR634 (A2862) | -II1 | Y | N | Y | Y? | ND | DD, MR, SD | N. Eur. | 7 | c.878A>C (h) | p.Q293P | 261/5,626 (4.6%) | All pat seq | Present study | 2.167 |
| -II2 | Y | N | Y | Y | N | MC, MD, SS | |||||||||
| A3260 | -II1 | N | Y | ND | N | Y | PSp, SI | USA | 9 | c.2983C>T (h) | p.R826C | 1,575/25,567 (6.2%) | All pat seq | Present study | 2.257 |
| A3227 | -II1 | N | N | Y | N | Y | BD, MR, PHP, SS | Egypt | 10 | c.1590A>C (h) | p.R530S | 102/11,606 (0.9%) | All pat seq | Present study | 1.686 |
| 12 | c.1507G>A (h) | p.V503M | 509/37,380 (1.4%) | All pat seq | Present study | 1.430 | |||||||||
ASD atrial septum defect, ATX ataxia, BD brachydactyly, DD developmental delay, DF dysmorphic features, HAP high arched palate, HNP herniated nucleus pulposus, MC macrocephaly, MD motor delay, MR mental retardation, MY (severe) myopia, OB overbite, PHP pseudohypoparathyroidism, PSp polysplenia, SD speech delay, SDys sensory dysesthesia, SI situs inversus, SS short stature, STBI strabismus, Sz seizures, ND no data available, N. Eur. Northern Europe
Accession numbers: BBS1, NM_024649; BBS2, NM_031885; BBS3, NM_177976; BBS4, NM_033028; BBS5, NM_152384; BBS6, NM_018848; BBS7, NM_176824; BBS8, NM_198309.2; BBS9, NM_198428; BBS10, NM_024685; BBS11, NM_012210; BBS12, NM_152618
Mutation numbering is based on the cDNA position in reference sequences indicated in Table 1 with +1 corresponding to the A of the ATG translation initiation codon. All changes were absent in the healthy control pool (96 HRC-1 individuals) and the “1,000 genomes project” (180 individuals)
The mutation carrier assignment was performed by heteroduplex based CEL I endonuclease screening (“CEL I”) or by direct Sanger sequencing of the respective 21 DNA samples (“All pat seq”). If initially only one mutated allele was found, all exons of the respective gene were sequenced (“All exon seq”)
Unpublished mutation analysis of family AR755 (A2867) showed the presence of a homozygous change in BBS1 (p.M390R)