Anemia, and Situs inversus totalis

Nephronophthisis is an autosomal recessive cystic kidney disease that leads to renal failure in childhood or adolescence. It is the most frequent genetic cause of renal failure in children. NPHP may be combined with extrarenal manifestations, such as liver fibrosis, situs inversus, or cardiac malformations. When nephronophthisis is combined with retinitis pigmentosa, the disorder is known as Senior-Loken syndrome (SLSN1 ); when it is combined with cerebellar vermis hypoplasia, the disorder is known as Joubert syndrome (JBTS1 ); and when it is combined with multiple developmental and neurologic abnormalities, the disorder is often known as Meckel-Gruber syndrome (MKS1 ). Because most NPHP gene products localize to the cilium or its associated structures, nephronophthisis and the related syndromes have been termed 'ciliopathies' (summary by Hoff et al., 2013).Clinical features of familial juvenile nephronophthisis include anemia, polyuria, polydipsia, isosthenuria, and death in uremia. Simms et al. (2009) provided a detailed review of nephronophthisis, including a discussion of clinical features and molecular genetics. Genetic Heterogeneity of NephronophthisisNPHP2 (OMIM ) is caused by mutation in the INVS gene (OMIM ) on chromosome 9q31; NPHP3 (OMIM ) is caused by mutation in the NPHP3 gene (OMIM ) on chromosome 3q22; NPHP4 (OMIM ) is caused by mutation in the NPHP4 gene (OMIM ) on chromosome 1p36; NPHP7 (OMIM ) is caused by mutation in the GLIS2 gene (OMIM ) on chromosome 16p13; NPHP9 (OMIM ) is caused by mutation in the NEK8 gene (OMIM ) on chromosome 17q11; NPHP11 (OMIM ) is caused by mutation in the TMEM67 gene (OMIM ) on chromosome 8q22; NPHP12 (OMIM ) is caused by mutation in the TTC21B gene (OMIM ) on chromosome 2q24; NPHP13 (OMIM ) is caused by mutation in the WDR19 gene (OMIM ) on chromosome 4p14; NPHP14 (OMIM ) is caused by mutation in the ZNF423 gene (OMIM ) on chromosome 16; NPHP15 (OMIM ) is caused by mutation in the CEP164 gene (OMIM ) on chromosome 11q; NPHP16 (OMIM ) is caused by mutation in the ANKS6 gene (OMIM ) on chromosome 9q22; NPHP18 (OMIM ) is caused by mutation in the CEP83 gene (OMIM ) on chromosome 12q22; NPHP19 (OMIM ) is caused by mutation in the DCDC2 gene (OMIM ) on chromosome 6p22; and NPHP20 (OMIM ) is caused by mutation in the MAPKBP1 gene (OMIM ) on chromosome 15q13.

NEPHRONOPHTHISIS 1; NPHP1 Is also known as nephronophthisis, familial juvenile|nph1

• Growth delay
• Anemia
• Hypertension
• Renal insufficiency
• Rod-cone dystrophy

SOURCES: OMIM ORPHANET MESH MENDELIAN

NEPHRONOPHTHISIS 3; NPHP3 Is also known as nph3

• Low-set ears
• Anemia
• Respiratory insufficiency
• Renal insufficiency
• Dilatation

SOURCES: OMIM MESH MENDELIAN

NEPHRONOPHTHISIS 2; NPHP2 Is also known as nph2

• Global developmental delay
• Anemia
• Hypertension
• Hepatomegaly
• Respiratory insufficiency

SOURCES: OMIM MESH MENDELIAN

Transaldolase deficiency is an inborn error of the pentose phosphate pathway that presents in the neonatal or antenatal period with hydrops fetalis, hepatosplenomegaly, hepatic dysfunction, thrombocytopenia, anemia, and renal and cardiac abnormalities.

TRANSALDOLASE DEFICIENCY Is also known as taldo deficiency|eyaid syndrome

• Global developmental delay
• Growth delay
• Failure to thrive
• Abnormal facial shape
• Low-set ears

SOURCES: MESH OMIM ORPHANET MENDELIAN

Thiamine-responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type I diabetes mellitus, and sensorineural deafness.

THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA SYNDROME Is also known as thmd1|trma|thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural deafness|rogers syndrome|thiamine-responsive myelodysplasia|thiamine metabolism dysfunction syndrome 1 (megaloblastic anemia, diabetes mellitus, and deafness type

• Seizures
• Global developmental delay
• Short stature
• Hearing impairment
• Microcephaly

SOURCES: MESH ORPHANET OMIM MENDELIAN

Johanson-Blizzard syndrome (JBS) is a multiple congenital anomaly characterized by exocrine pancreatic insufficiency, hypoplasia/aplasia of the nasal alae, hypodontia, sensorineural hearing loss, growth retardation, anal and urogenital malformations, and variable intellectual disability.

JOHANSON-BLIZZARD SYNDROME Is also known as jbs|nasal alar hypoplasia, hypothyroidism, pancreatic achylia, and congenital deafness

• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET OMIM MESH MENDELIAN

VACTERL/VATER is an association of congenital malformations typically characterized by the presence of at least three of the following: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities.

VACTERL/VATER ASSOCIATION Is also known as vacterl association|vater association

• Intellectual disability
• Global developmental delay
• Scoliosis
• Growth delay
• Failure to thrive

SOURCES: ORPHANET OMIM MENDELIAN

• Ventricular septal defect
• Atrial septal defect
• Abnormality of cardiovascular system morphology
• Abnormal heart morphology
• Abnormal cardiac septum morphology

SOURCES: MESH OMIM MENDELIAN

Ss blood group antigens reside on the red-cell glycoprotein GYPB. The S and s antigens result from a polymorphism at amino acid 29 of GYPB, where S has met29 and s has thr29. The U antigen refers to a short extracellular sequence in GYPB located near the membrane. GYPB, glycophorin A (GYPA ), and glycophorin E (GYPE ) are closely linked on chromosome 4q31. Antigens of the MN blood group (OMIM ) reside on GYPA. The M and N antigens differ at amino acids 1 and 5 of GYPA, where M is ser-ser-thr-thr-gly, and N is leu-ser-thr-thr-glu. The N terminus of GYPB is essentially identical to that of GYPA except that it always expresses the N antigen, denoted 'N' or N-prime. Recombination and gene conversion between GYPA, GYPB, and GYPE lead to hybrid glycophorin molecules and generation of low-incidence antigens. Thus, the MN and Ss blood groups are together referred to as the MNSs blood group system (see {111300}). Recombination results in 3 glycophorin-null phenotypes: En(a-) cells lack GYPA due to recombination between GYPA and GYPB; GYPB-negative (S-s-U-) cells lack GYPB due to recombination in GYPB; and M(k) cells (M-N-S-s-U-) lack both GYPA and GYPB due to recombination between GYPA and GYPE. Individuals with glycophorin-null phenotypes have decreased sialic acid content and increased resistance to malarial infection (see {611162}). GYPA and GYPB are not essential for red-cell development or survival, and GYPA- and GYPB-null phenotypes are not associated with anemia or altered red-cell function (review by Cooling, 2015).

BLOOD GROUP, SS; SS Is also known as ss blood group

• Neoplasm
• Anemia

SOURCES: OMIM MENDELIAN

Primary ciliary dyskinesia is an autosomal recessive disorder resulting from loss of normal ciliary function. Kartagener (pronounced KART-agayner) syndrome is characterized by the combination of primary ciliary dyskinesia and situs inversus, and occurs in approximately half of patients with ciliary dyskinesia. Since normal nodal ciliary movement in the embryo is required for normal visceral asymmetry, absence of normal ciliary movement results in a lack of definitive patterning; thus, random chance alone appears to determine whether the viscera take up the normal or reversed left-right position during embryogenesis. This explains why approximately 50% of patients, even within the same family, have situs inversus (Afzelius, 1976; El Zein et al., 2003).

CILIARY DYSKINESIA, PRIMARY, 3; CILD3 Is also known as ciliary dyskinesia, primary, 3, with or without situs inversus

• Recurrent respiratory infections
• Dyskinesia
• Situs inversus totalis
• Akinesia
• Ciliary dyskinesia

SOURCES: MESH OMIM MENDELIAN