Table 1.
Patients with Likely Pathogenic TRPM1 Mutations
| Index Patient, Location, Family Members | Ethnicity | Exon | Nucleotide Exchange | Allele State | Protein Effect | Control Alleles (Mut/WT) | Phenotype Index |
|---|---|---|---|---|---|---|---|
| CIC00238: Paris, France | Portuguese-French | 12 | c.1418G>C | hom? | p.Arg473Pro | 0/286 | cCSNB, myopia, nystagmus, strabismus |
| unaff. father CIC03424 | 12 | c.1418G>C | het | p.Arg473Pro | |||
| unaff. mother CIC03423 | - | no | - | - | |||
| unaff. sister CIC03421 | - | no | - | - | |||
| unaff. sister CIC03422 | - | no | - | - | |||
| aff. sister CIC03452 | 12 | c.1418G>C | hom? | p.Arg473Pro | cCSNB, myopia, nystagmus, strabismus | ||
| 4497a, II-1: Tuebingen, Germany | German | 3 | c.31C>T | het | p.Gln11X | 0/352 | cCSNB, nystagmus, myopia |
| 4 | c.296T>C | het | p.Leu99Pro | 0/224 | |||
| unaff. father 4608, I-1 | 4 | c.296T>C | het | p.Leu99Pro | |||
| unaff. mother 4610, I-2 | 3 | c.31C>T | het | p.Gln11X | |||
| unaff. sister 4600, II-2 | - | no | - | - | |||
| unaff. sister 4712, II-4 | 3 | c.31C>T | het | p.Gln11X | |||
| unaff. brother 4740, II-3 | 3 | c.31C>T | het | p.Gln11X | |||
| 691: Tuebingen, Germany | Turkish | 20 | c.2567G>A | hom? | p.Trp856X | 0/366 | cCSNB, myopia, nystagmus,strabismus |
|
8214: Tuebingen, Germany |
German |
10 | c.1197G>A | het | c.Pro399Pro/splice defect? | 0/350 | cCSNB, myopia, strabismus |
| 26 | c.3491delA | het | p.Gln1164ArgfsX31 | 0/266 | |||
| CIC00612: Paris, France | French | 4 | c.215A>G | het | p.Tyr72Cys | 0/210 | cCSNB, myopia, nystagmus, strabismus |
| 24 | c.3094G>T | het | p.Glu1032X | 0/370 | |||
| unaff. mother: CIC03359 | 24 | c.3094G>T | het | p.Glu1032X | |||
| unaff. brother: CIC03360 | - | no | - | - | |||
| 23625a, II-3: Lausanne, Switzerland | Italian | 4 | c.215A>G | het | p.Tyr72Cys | 0/210 | cCSNB, myopia |
| int4 | c.428-3C>G | het | splice defect | 0/298 | |||
| unaff. father 23628, I-1 | 4 | c.215A>G | het | p.Tyr72Cys | |||
| unaff. mother 23728, I-2 | int4 | c.428-3C>G | het | splice defect | |||
| unaff. brother CIC03365, II-1 | - | no | - | ||||
| unaff. brother CIC03364, II-2 | 4 | c.215A>G | het | p.Tyr72Cys | |||
|
758.01: Giessen, Germany |
German |
int20 | c.2634+1G>A | het | splice defect | 0/366 | cCSNB |
| 27 | c.3834C>T | het | p.Asn1278Asn | 0/304 | |||
| D0704708a, II-3: Ghent, Belgiumb | Flemish-Belgian | 2 | c.1-27C>T (70+TRPM1) or c.40C>T (92+TRPM1) | hom | 5′ UTR expression defect or p.Arg14Trp | 0/348 | cCSNB, strabismus, hypermetropia |
| unaff. father CIC03386, I-1 | 2 | ″ | het | 5′ UTR expression defect or p.Arg14Trp | |||
| unaff. mother D0704709, I-2 | 2 | ″ | het | 5′ UTR expression defect or p.Arg14Trp | |||
| unaff. sister CIC03389, II-1 | 2 | ″ | het | 5′ UTR expression defect or p.Arg14Trp | |||
| unaff. sister CIC03390, II-2 | 2 | ″ | het | 5′ UTR expression defect or p.Arg14Trp | |||
| unaff. brother CIC03391, II-3 | - | no | - | ||||
| 14101: Philadelphia, PA, USA | Austrian-Russian-Ashkenazi Jewish | 18 | c.2322T>A | het | p.Tyr774X | 0/380 | cCSNB, myopia |
| ? | ? | - | ? | ||||
| unaff. father 19037 | ? | ? | - | ? | |||
| unaff. mother 19038 | 18 | c.2322T>A | het | p.Tyr774X | |||
| 10731: Berlin, Germany | German | 14 | c.1622T>A | het | p.Met541Lys | 0/214 | cCSNB, myopia |
| ? | ? | - | ? | ||||
Index patients are presented in bold. Abbreviations are as follows: Mut, mutated; het, heterozygous; hom, homozygous; unaff., unaffected; aff., affected. CSNB mutations are annotated according to the recommendation of the Human Genome Variation Society, with nucleotide position +1 corresponding to the A of the translation-initiation codon ATG in the cDNA nomenclature RefSeq NM_002420.4, 70+TRPM1. For Exon 0 and Exon 1′, the respective A of the new translation initiation codon ATG was used.
a
See Figures 3A and 3B.
b
27533 Diagnostic: Zurich, Switzerland.