Anemia, and Strabismus

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

• Anemia
• Hyperpigmentation of the skin

SOURCES: OMIM MENDELIAN

MN antigens reside on GYPA, one of the most abundant red-cell glycoproteins. The M and N antigens are 2 autosomal codominant antigens encoded by the first 5 amino acids of GYPA and include 3 O-linked glycans as part of the epitope. M and N differ at amino acids 1 and 5, where M is ser-ser-thr-thr-gly, and N is leu-ser-thr-thr-glu. M is the ancestral GYPA allele and is common in all human populations and Old World apes. GYPA, glycophorin B (GYPB ), and glycophorin E (GYPE ) are closely linked on chromosome 4q31. 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. Antigens of the Ss blood group (OMIM ) reside on GYPB, and 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 or MNS blood group system. The U antigen refers to a short extracellular sequence in GYPB located near the membrane. 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, MN; MN Is also known as mn blood group

• Neoplasm
• Anemia
• Leukemia

SOURCES: OMIM MENDELIAN

X-linked sideroblastic anemia and ataxia (XLSA-A) is a rare syndromic, inherited form of sideroblastic anemia (see this term) characterized by mild to moderate anemia (with hypochromia and microcytosis) and early-onset, non- or slowly progressive spinocerebellar ataxia.

X-LINKED SIDEROBLASTIC ANEMIA AND SPINOCEREBELLAR ATAXIA Is also known as x-linked sideroblastic anemia with ataxia|xlsa-a|pagon-bird-detter syndrome

• Global developmental delay
• Scoliosis
• Ataxia
• Nystagmus
• Strabismus

SOURCES: MESH OMIM ORPHANET MENDELIAN

• Global developmental delay
• Growth delay
• Nystagmus
• Strabismus
• Anemia

SOURCES: OMIM MENDELIAN

Mitochondrial complex III deficiency, nuclear type 8, is an autosomal recessive disorder characterized by progressive neurodegeneration with onset in childhood. Affected individuals may have normal or delayed early development, and often have episodic acute neurologic decompensation and regression associated with febrile illnesses. The developmental regression results in variable intellectual disability and motor deficits, such as hypotonia, axial hypertonia, and spasticity; some patients may lose the ability to walk independently. Laboratory studies show increased serum lactate and isolated deficiency of mitochondrial complex III in skeletal muscle and fibroblasts. Brain imaging shows a characteristic pattern of multifocal small cystic lesions in the periventricular and deep cerebral white matter (summary by Dallabona et al., 2016).For a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (OMIM ).

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Ataxia
• Nystagmus

SOURCES: OMIM MENDELIAN

Type II Gaucher disease is an acute neuronopathic form of the disorder with onset in infancy and death often by 2 years of age. Patients are usually normal at birth, but develop hepatosplenomegaly, developmental regression, and growth arrest within a few months of age. Neurologic deterioration proceeds rapidly, with cranial nerve and extrapyramidal tract involvement (Stone et al., 2000).

GAUCHER DISEASE, TYPE II Is also known as gaucher disease, acute neuronopathic type|gd ii

• Seizures
• Global developmental delay
• Failure to thrive
• Strabismus
• Spasticity

SOURCES: OMIM MENDELIAN

Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations is a rare cancer-predisposing syndrome, associated with the D1 subgroup of Fanconi anemia (FA), characterized by progressive bone marrow failure, cardiac, brain, intestinal or skeletal abnormalities and predisposition to various malignancies. Bone marrow suppression and the incidence of developmental abnormalities are less frequent than in other FA, but cancer risk is very high with the spectrum of childhood cancers including Wilms tumor, brain tumor (often medulloblastoma) and ALL/AML.

INHERITED CANCER-PREDISPOSING SYNDROME DUE TO BIALLELIC BRCA2 MUTATIONS Is also known as fad1

• Short stature
• Microcephaly
• Growth delay
• Neoplasm
• Failure to thrive

SOURCES: ORPHANET OMIM MESH MENDELIAN

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hypertelorism

SOURCES: OMIM MENDELIAN

Syndromic optic atrophy, also known as DOA+ syndrome, is a neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia (PEO), muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010).

OPTIC ATROPHY WITH OR WITHOUT DEAFNESS, OPHTHALMOPLEGIA, MYOPATHY, ATAXIA, AND NEUROPATHY Is also known as dominant optic atrophy plus syndrome|doa+

• Seizures
• Hearing impairment
• Ataxia
• Strabismus
• Sensorineural hearing impairment

SOURCES: OMIM MENDELIAN