The variants in PLXNB2 identified in six families and the disease features observed
| Patient (sex/age range) | Zygosity and variants (NM_012401.4, NP_036533.2) | Phenotype | ||||
| Auditory | Dental | Developmental/neurological | Vision | Other | ||
| Family 1 II:3 (M/12–18) | Homozygous c.2413A>T: p.(Ile805Phe); c.2413A>T: p.(Ile805Phe) | SNHL | AI, conical permanent incisors | Global developmental delay, moderate intellectual disability | Myopia, horizontal nystagmus (congenital cataract due to CRYBB3 variant) | Ear lobe skin blind-ended tracts |
| Family 1 II:6 (M/19–21) | Homozygous c.2413A>T: p.(Ile805Phe); c.2413A>T: p.(Ile805Phe) | SNHL; labyrinthine malformation | AI, conical permanent incisors | Global developmental delay, epilepsy, moderate intellectual disability | Severe myopia with scattered papillae, horizontal nystagmus, macular atrophy | Ear lobe skin blind-ended tracts, unilateral renal agenesis, pyloric stenosis, asthma, recurrent bronchitis, intrauterine growth retardation, finger pads, watch glass toenails, overweight |
| Family 2 IV:2 (M/12–18) | Homozygous c.2248G>A: p.(Asp750Asn); c.2248G>A: p.(Asp750Asn) | SNHL | AI | Intellectual disability | No obvious abnormality, not examined | |
| Family 3 II:1 (M/6–11) | Compound heterozygous c.750C>A: p.(Cys250*); c.3117G>A: p.(Thr1039=) | SNHL (mild) 500–4000 Hz | AI with hypoplasia | Normal | Developmental macular abnormality with pale fundus, attenuated blood vessels, high myopia, nystagmus, microcornea | Ear lobe skin blind-ended tracts, cleft palate, hypertelorism, keratopathy |
| Family 4 II:1 (F/19–21) | Compound heterozygous c.2606del: p.(Phe869Serfs*45); c.3982_3986del: p.(Phe1328His*65) | SNHL | AI; missing upper permanent lateral incisors | Normal | No obvious abnormality, not examined | Ear lobe skin blind-ended tracts, bilateral primary lower limb lymphoedema (onset aged 3), nevus, cellulitis |
| Family 5 II:1 (F/50–59) | Homozygous c.5197-337_5310del: p.(Asp1733_Arg1779del); c.5197-337_5310del: p.(Asp1733_Arg1779del) | SNHL | AI | Mild/moderate intellectual disability | No obvious abnormality, not examined | Bilateral primary lower limb lymphoedema |
| Family 5 II:2 (M/50–59) | Homozygous c.5197-337_5310del: p.(Asp1733_Met1770del); c.5197-337_5310del: p.(Asp1733_Met1770del) | SNHL | AI | Intellectual disability | No obvious abnormality, not examined | Unilateral lymphoedema of one foot |
| Family 6 III:1 (M/2–5) | Homozygous c.4609G>A: p.(Gly1537Ser); c.4609G>A: p.(Gly1537Ser) | Could not be assessed; no current indication of hearing loss | Clinical tooth failure (cause unclear); could not be assessed further | Profound intellectual disability, non-verbal, autistic features, hyperactive behaviour | Strabismus, no other obvious abnormality, could not be assessed | Mild generalised muscular hypotonia |
Splicing prediction tools suggest that exon 35 is entirely skipped leading to p.(Asp1733_Arg1779del) instead of p.(Asp1733_Met1770del) as would be predicted from the proportion of the gene deleted. Age ranges are shown for individuals to maintain anonymity. Age of onset was from birth unless otherwise stated. Variants are based on genome build GRCh37 and PLXNB2 transcript ENST00000359337.9, NM_012401.4 and PLXNB2 protein ENSP00000352288.4, NP_036533.2.
AI, amelogenesis imperfecta; SNHL, sensorineural hearing loss.