Table 1 Genotype and clinical phenotype of novel patients
NBAS variants (NM_015909.3; NP_056993.2) | Main clinical features | Other symptoms | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patient ID | Subgroup | Allele 1 | Region of NBAS affected by allele 1 | Allele 2 | Region of NBAS affected by allele 2 | Abnormality of the liver | Abnormality of growth (short stature) | Abnormality of the skeletal system | Abnormality of the nervous system | Abnormality of the integument (cutis laxa) | Abnormality of the immune system | Abnormality of the musculature (hypotonia or atrophy) | |
NBAS 46 | ß-propeller (combined) | c.(284C > T); p.(Ala95Val) | ß-propeller | c.(2802G > A); p.(Trp934*) | n.a. | ALF | Y | Cervical instability, reduced bone mineral density | Motor delay | Y | Low IgG | Y | High pitched voice |
NBAS 82 | c.(812T > C); p.(Leu271Pro) | ß-propeller | c.(812T > C); p.(Leu271Pro) | ß-propeller | ALF | Y | N | Motor delay | N | Low IgG | Y | Protuberant abdomen, high pitched voice | |
NBAS 7 | c.(1241C > T); p.(Ser414Phe) | ß-propeller | c.(2950delA); p.(Ile984Leufs*8) | n.a. | ALF | Y | Reduced bone mineral density, delayed closure of fontanelle, pectus excavatum, long thin fingers, short metacarpals, clinodactyly, multiple Wormian bones, severe scoliosis with spinal cord compression in teens, pathologic fracture, joint laxity | Optic atrophy | Y | Low IgG, PHA | Y | Insulin dependent diabetes mellitus (onset at 8 years), chronic lung disease with oxygen dependency and BiPAP respiratory support, high pitched voice | |
NBAS 8 | c.(1241C > T); p.(Ser414Phe) | ß-propeller | c.([6236 + 1_6237–1]_[6432 + 1_6433–1]del); p.(Glu2080*) | n.a. | cELT | Y | Reduced bone mineral density, delayed closure of fontanelle, low arch and flatfoot, flat cheekbone, pectus excavatum, long digits | Optic atrophy, motor delay | Y | PHA | Y | Relative macrocephaly, decreased serum IGF1 and IGFBP3, high pitched voice | |
NBAS 13 | c.(1549C > T); p.(Arg517Cys) | Between ß-propeller and Sec39 | c.(5041_5048del); p.(Ser1681Glnfs*37) | n.a. | ALF | N | Reduced bone mineral density, pectus excavatum, long digits, scoliosis, pathologic fracture | N | N | Low IgG | Y | Cataract and dislocation of the lens at 1 year, recurrent malaise, nephrolithiasis at 8 years, high pitched voice | |
NBAS 12 | c.(1550G > A); p.(Arg517His) | Between ß-propeller and Sec39 | c.(6805G > T); p.(Glu2269*) | n.a. | ALF | N | N | N | N | N | N | Deceased at 3 years | |
NBAS 64 | c.(1550G > A); p.(Arg517His) | Between ß-propeller and Sec39 | c.(6805G > T); p.(Glu2269*) | n.a. | ALF | N | N | N | N | N | Not reported | Preemptive family testing | |
NBAS 51 | Sec39 (ILFS2) | c.(2191A > C); p.(Thr731Pro) | Sec39 | c.(2191A > C); p.(Thr731Pro) | Sec39 | ALF | Y | N | N | N | N | N | Liver transplantation at 1 year; deceased at 15 years |
NBAS 55 | c.(2330C > A); p.(Pro777His) | Sec39 | c.(2330C > A); p.(Pro777His) | Sec39 | ALF | N | N | N | N | N | N | Elevated 3-methylglutaconic in urine, vitamin D deficiency | |
NBAS 56 | c.(2330C > A); p.(Pro777His) | Sec39 | c.(2330C > A); p.(Pro777His) | Sec39 | ALF | N | N | N | N | N | N | Vitamin D deficiency | |
NBAS 68 | c.(2809C > G); p.(Pro937Ala) | Sec39 | c.([5138 + 1_5139-1]_7116del); p.(?) | n.a. | ALF | Y | N | N | N | N | N | ||
NBAS 54 | c.(2819A > C); p.(His940Pro) | Sec39 | c.(2819A > C); p.(His940Pro) | Sec39 | ALF | N | N | N | N | Reduced NK cells | N | ||
NBAS 9 | c.(2951T > G); p.(Ile984Ser) | Sec39 | c.(2827G > T); p.(Glu943*) | n.a. | ALF | Y | Brachycephaly, long digits, clinodactyly, delayed skeletal maturation | N | N | PHA | N | Precocious puberty, high pitched voice | |
NBAS 69 | c.(3164T > C); p.(Leu1055Pro) | Sec39 | c.([5027 + 1_5028-1]_[5724 + 1_5725-1]del); p.(Glu1676Aspfs*10) | n.a. | ALF | N | N | N | N | Low IgG | N | ||
NBAS 84 | c.(3363A > G); p.(Ile1121Met) | Sec39 | c.(513 + 2T > C); p.(?) | n.a. | ELT | Y | N | N | N | Low IgA | Not reported | ||
NBAS 58 | c.(3386C > T); p.(Ser1129Phe) | Sec39 | c.(3386C > T); p.(Ser1129Phe) | Sec39 | ALF | N | N | N | N | N | N | Elevated 3-methylglutaconic and 3-methylglutaric in urine | |
NBAS 59 | c.(3386C > T); p.(Ser1129Phe) | Sec39 | c.(3386C > T); p.(Ser1129Phe) | Sec39 | ALF | N | N | N | N | N | Not reported | Elevated 3-methylglutaconic and 3-methylglutaric in urine | |
NBAS 60 | c.(3534C > A); p.(Ser1178Arg) | Sec39 | c.(1342-6A > G); p.(?) | n.a. | ALF | N | N | N | N | Low IgG, reduced NK cells | N | During crisis: seizures, cholecystitis, truncal exanthema, hypophosphatemia, anemia, lymphopenia, significant decrease of neutrophils | |
NBAS 53 | c.(3602A > C); p.(Gln1201Pro) | Sec39 | c.(3602A > C); p.(Gln1201Pro) | Sec39 | ALF | N | N | N | N | N | N | Liver transplantation at 4 years | |
NBAS 50 | C-terminal (SOPH) | c.(5741G > A); p.(Arg1914His) | C-terminal | c.(1528C > T); p.(Arg510*) | n.a. | cELT | Y | Delayed skeletal maturation, delayed closure of fontanelle, brachycephaly, clinodactyly | ID, motor delay | Y | Low IgG | Y | |
NBAS 62 | c.(5740C > G); p.(Arg1914Gly) | C-terminal | c.(6877delC); p.(Leu2293Cysfs*9) | n.a. | ALF | Y | Reduced bone mineral density, delayed closure of fontanelle, flat cheekbone, short digits, delayed skeletal maturation | Optic atrophy, motor delay | Y | Low IgG, PHA | Y | High pitched voice | |
NBAS 14 | c.(5761G > C); p. (Ala1921Pro) | C-terminal | c.(686dupT); p.(Ser230Glnfs*4) | n.a. | cELT | N | N | N | N | Low IgG, PHA | N | ||
NBAS 11 | c.(6840G > T); p.(?) | C-terminal | c.(6840G > T); p.(?) | C-terminal | ELT | Y | Syndactyly of second and third toe on both feet, flat cheekbone, delayed skeletal maturation | Optic atrophy, motor delay | N | Low IgG, PHA | N | Rotary nystagmus, high pitched voice | |
NBAS 57 | c.(6966_6969delinsTC); p.(Gln2322Hisfs*18) | C-terminal | c.(5547delC); p.(Trp1850Glyfs*32) | n.a. | ELT | N | N | Optic atrophy, motor delay | N | Low IgG, reduced NK cells | Not reported | Premature birth, recurrent bacterial pneumonia (with persistent right middle lobe atelectasis) | |
NBAS 61 | c.(767G > A); p.(Cys256Tyr) | ß-propeller | c.(2012T > G); p.(Phe671Cys) | Between ß-propeller and Sec39 | ELT | Y | N | ID, motor delay | Not reported | N | N | Genetically diagnosed Williams–Beuren syndrome; Williams–Beuren syndrome like dysmorphism | |
NBAS 83 | c.(2535G > T); p.(Trp845Cys) | Sec39 | c.(5761G > C); p.(Ala1921Pro) | C-terminal | ALF | Y | Not reported | N | Not reported | Not reported | Not reported | ||
