Table 4 Recessive inheritance in dominant disease genes
Patient no. | Observed recessive phenotype | Gene | Zygosity | Variant(s) | Dominant phenotype (OMIM) | Parental health status | Comparison with AD phenotype | Previous reports of recessive inheritance |
|---|---|---|---|---|---|---|---|---|
574 | Absent lower limbs; Absent pelvic bones; Hypoplastic sacrum; Severe lung hypoplasia; Ambiguous genitalia | TBX4 | Hom | NM_001321120.2c.339T>A p.(Tyr113*) | Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension | Mildly affected | More severe | Noa |
751 | Multiple skeletal abnormalities of lower limbs with bowing of femurs and polydactyly and syndactyly of all four limbs; Imperforate anus; Rectal stenosis; Anocutaneous fistula; Polysplenia | GLI3 | Hom | NM_000168.5c.1927C>T p.(Arg643*) | Greig cephalopolysyndactyly syndrome Pallister–Hall syndrome Polydactyly, postaxial, types A1 and B Polydactyly, preaxial, type IV | Mildly affected | More severe | Noa |
1427 | Aborted fetus with polycystic kidney | BICC1 | Hom | NM_001080512.3c.611C>T p.(Pro204Leu) | Renal dysplasia, cystic, susceptibility to | Healthy | More severe | No |
647 | Onset at the age of 21-year with a speech problem and attention deficit; Mild muscle spasticity, upper limbs, mild; Drooling; Parkinsonian gait; Aggression; Brain MRI: generalized atrophic changes | DCTN1 | Hom | NM_004082.5c.2267C>T p.(Ala756Val) | Neuronopathy, distal hereditary motor, type VIIB Perry syndrome Amyotrophic lateral sclerosis, susceptibility to | Unknownb | Similar | No |
1091 | Developmental regression; Hearing loss, severe to profound; Abnormal teeth; Asymmetric kidneys; Loss of ambulation | KCNC3 | Hom | NM_004977.3c.2060C>T p.(Pro687Leu) | Spinocerebellar ataxia 13 | Unknownb | Similar | No |
41 | Recurrent bone fractures; Growth failure; Delayed puberty | COL1A2 | Hom | NM_000089.4c.910G>A p.(Gly304Ser) | Combined osteogenesis imperfecta and Ehlers–Danlos syndrome 2 Ehlers–Danlos syndrome arthrochalasia type, 2 Osteogenesis imperfecta, type II Osteogenesis imperfecta, type III Osteogenesis imperfecta, type IV | Mildly affected | More severe | Yes |
1077 | Face and hands Lesions; Skin biopsy: more compatible with progeria | PPOX | Hom | NM_000309.5c.848T>C p.(Ile283Thr) | Porphyria variegata | Unknownb | More severe | Yes |
1172 | Hypertension; Cystic kidney, bilateral; Urinary tract infections | PKD1 | Hom | NM_001009944.2c.1360C>T p.(Arg454Cys) | Polycystic kidney disease 1 | Unknownb | Similar | Yes |
1068 | Lower & upper limbs neuropathy; Difficulty walking; EDX: severe chronic demyelinating sensory-motor polyneuropathy with secondary axonal loss | HARS1 | Compound Het Compound Het | NM_002109.6c.90+4A>C NM_002109.6c.1393A>C p.(Ile465Leu) | Charcot-Marie-Tooth disease, axonal, type 2W | Unknownb | Similar | Yes |
1372 | Hearing loss | MITF | Hom | NM_000248.4c.721T>C p.(Trp241Arg) | Tietz albinism-deafness syndrome Waardenburg syndrome, type 2A | Unknownb | Milder (Non-syndromic) | Yes |
1430 | Onset at the age of 4 months with Intractable epilepsy, infantile spasm; Developmental delay; Mental retardation; Impaired swallowing (NGT feeding); Brain MRI showed brain atrophy suggestive of neurodegenerative disorders; Abnormal EEG | UFSP2 | Hom | NM_018359.5c.344T>A p.(Val115Glu) | Hip dysplasia, Beukes type Spondyloepimetaphyseal dysplasia, Di Rocco type | Unknownb | Distinct | Yes |
