Table 2

Identified KIF21A (NM_001173464.2) variants and associated clinical features

Patient ID #Family #Gender/age at TOPAffected geneDNA changePredicted AA changeVariant classification (ACMG)ZygosityOMIM phenotype (mode of inheritance)Aetiological classification (OMIM diseases)Prenatal abnormalitiesJoint contracturesDysmorphic featuresNeurological abnormalitiesOther features
F22:II.122M/TOP (24 WGA)KIF21Ac.(1346T>A);(1346T>A)p.((Leu449*));((Leu449*))Candidate gene, likely pathogenicHomozygous#135700 (AD), novel for AR pendingLikely neurogenic (disease name to be determined)RFM, polyhydramnios, scalp oedema, pulmonary hypoplasia, missing stomach filling, diaphragmatic protrusion, thoracic kyphoscoliosisElbows, wrists, fingers, knees, ankles, talipes equinovarus (bilateral)Hypertelorism, retrognathia, cleft palate, flat broad nose, low-set earsHypotrophy of lower leg musclesInternally rotated shoulders, straight ribs, narrow long tubular bones
F22:II.222F/TOP (26 WGA)KIF21Ac.(1346T>A);(1346T>A)p.((Leu449*));((Leu449*))Candidate gene, likely pathogenicHomozygous#135700 (AD), novel for AR pendingLikely neurogenic (disease name to be determined)RFM, polyhydramnios, IUGR, scalp oedema, thoracic hypoplasia, hydrothorax, ascites, missing stomach filling, diaphragmatic protrusionElbows, fingers, knees, talipes equinovarus (bilateral)Microglossia, mircognathia and retrognathia, cleft palate, high-arched palate, low-set earsJejunal perforation, dilated tortuous ureter (bilateral), internally rotated shoulders, thoracic scoliosis, additional cervical rib, straight ribs, narrow long tubular bones, femoral anteversion (bilateral), genu recurvatum (bilateral)
F22:II.422M/TOP (21 WGA)KIF21Ac.(1346T>A);(1346T>A)p.((Leu449*));((Leu449*))Candidate gene, likely pathogenicHomozygous#135700 (AD), novel for AR pendingLikely neurogenic (disease name to be determined)RFM, micrognathia, prenasal oedema, neck oedema, pulmonary hypoplasiaKnees, talipes equinovarus (bilateral)ND (autopsy not performed)
F23:II.123M/TOP (29 WGA)KIF21Ac.(2371del);(2371del)p.((Arg791Glufs*8));((Arg791Glufs*8))Candidate gene, likely pathogenicHomozygous#135700 (AD), novel for AR pendingLikely neurogenic (disease name to be determined)RFM, polyhydramnios, brachycephaly, scalp oedema, prenasal oedema, neck oedema, pulmonary hypoplasia, dextrocardia, gastrointestinal abnormalitiesFingers, wrists, talipes equinovarus (bilateral), rocker-bottom feetSkull deformation with protruding skull bones, micrognathia and retrognathia, clinodactyly of 2nd digit (bilateral)Cerebral ventriculomegalySevere pulmonary hypoplasia, dextrocardia, clenched hands with crossing fingers (bilateral)
F23:II.223F/TOP (28 WGA)KIF21Ac.(2371del);(2371del)p.((Arg791Glufs*8));((Arg791Glufs*8))Candidate gene, likely pathogenicHomozygous#135700 (AD), novel for AR pendingLikely neurogenic (disease name to be determined)RFM, polyhydramnios, scalp oedema, prenasal oedema, pulmonary hypoplasiaFingers, wrists, talipes equinovarus (bilateral)Micrognathia and retrognathia (autopsy not performed)
  • List of genetic variants and clinical details of individuals carrying bi-allelic variants in the candidate gene KIF21A. Provided information includes patient ID, family ID, gender, age at termination of pregnancy in WGA. Additionally, provided data include the affected gene, RefSeq ID, DNA change, AA change, variant classification (ACMG scores), gene-associated OMIM phenotype, mode of inheritance and zygosity.

  • The variant nomenclature is in accordance with Human Genome Variation Society standards.

  • AA, amino acid; ACMG, American College of Medical Genetics and Genomics; AD, autosomal dominant; AR, autosomal recessive; F, female; IUGR, intrauterine growth restriction; M, male; ND, no data; RFM, reduced fetal movements; TOP, termination of pregnancy; WGA, weeks of gestational age.