Autosomal recessive renal tubular dysgenesis: antenatal ultrasound scanning and molecular investigations

Figures

• 

  Fig. 1. Pedigree, schematic diagram, WES-CNV analysis, Sanger sequencing, and pathological examination of patients with autosomal recessive renal tubular dysgenesis caused by AGT deletion. (a) A pedigree illustrating individuals from family 1 with a homozygous AGT deletion, indicated by filled black symbols. (b) Schematic diagram of the c.830-619_1242 + 243delinsTTGCCTTGC mutation in the AGT gene. This mutation results from the deletion of nucleotides from c.830-619 to c.1242 + 243, which are replaced by nucleotides TTGCCTTGC. (c) Illustration of the deletion of AGT by WES-CNV: a homozygous deletion of the AGT gene in the fetus, while the couple is heterozygous for this deletion. (d) A 2870 bp deletion with a 9 bp insertion (indicated by the dashed box) was detected by Sanger sequencing in individual II-1, while individual II-3 does not carry the deletion. (e) pathological examination of II-2 revealed that the number of proximal convoluted tubules was small and poorly developed. AGT, angiotensinogen; CNV, copy number variation; WES, whole-exome sequencing.

• 

  Fig. 2. Prenatal ultrasound images of the fetus (II-1, II-2, and II-3) in family 1. Fetus II-1 with ARRTD at 30 weeks gestational age (wGA) shows slightly enlarged fetal kidneys with enhanced echogenicity, an underfilled bladder, and an amniotic fluid index (AFI) of 3.5 cm, with a depth (AFV) of 1.2 cm. Fetus II-2 with ARRTD at 23 weeks gestational age reveals normal-sized fetal kidneys; however, there is enhanced cortical echogenicity, a blurred corticomedullary boundary, and an absent bladder. The AFI was measured at 0.93 cm. Fetus II-3 at 23 wGA shows normal kidneys and a full bladder. The AFI is 16.09 cm, with a depth (AFV) of 4.75 cm. ARRTD, autosomal recessive tubular dysplasia; AFV, amniotic fluid volume.

• 

  Fig. 3. Pedigree, schematic diagram, WES-CNV analysis, Sanger sequencing, and three-dimensional structure diagram of patients with ARRTD caused by a heterozygous deletion of exons 3–4 and a heterozygous C.571C>T (p.Gln191Ter) mutation in the AGT gene. (a) A pedigree illustrating individuals from family 2 with compound heterozygous AGT mutations is represented by filled black symbols. (b) A schematic diagram of the compound heterozygous mutation in the AGT gene. This mutation results from a deletion of nucleotides ranging from c.830-619 to c.1242 + 243, which is replaced by the nucleotides TTGCCTTGC (indicated by the dashed box) in the AGT gene. Additionally, there is a heterozygous C.571C>T (p.Gln191Ter) mutation, represented by the red triangle, also within the AGT gene. (c) Illustration of the deletion of the AGT gene as detected by WES-CNV and Sanger sequencing: a heterozygous deletion of the AGT gene is present in both the fetus and the father, while the mother does not carry the deletion. (d) A heterozygous C.571C>T (p.Gln191Ter) mutation (indicated by a red triangle) was detected by Sanger sequencing in both the fetus and the mother, while the father does not carry the mutation.…

• 

  Fig. 4. Prenatal ultrasound images of the fetuses (II-1 and II-2) in family 2. Fetus II-1 with ARRTD at 24 weeks gestational age (wGA) shows normal kidneys, an unclear bladder, and an amniotic fluid index (AFI) of 2 cm, with a depth (AFV) of 1.3 cm. Fetus II-2 with ARRTD at 27 weeks gestational age (wGA) revealed normal kidneys, an underfilled bladder, and an AFI of 5.3 cm, with a depth (AFV) of 1.6 cm. There was increased renal blood flow resistance and reversed blood flow during full diastole. AFV, amniotic fluid volume. AFV, amniotic fluid volume; ARRTD, autosomal recessive tubular dysplasia.