Leukemia, and Muscular dystrophy

Autosomal recessive limb-girdle muscular dystrophy type 2J (LGMD2J) is a form of limb-girdle muscular dystrophy that usually has a childhood onset (but can range from the first to third decade of life) of severe progressive proximal weakness, eventually involving the distal muscles. Some patients may remain ambulatory but most are wheelchair dependant 20 years after onset.

AUTOSOMAL RECESSIVE LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 2J Is also known as lgmd2j|muscular dystrophy, limb-girdle, type 2j

• Cardiomyopathy
• Myopathy
• Elevated serum creatine phosphokinase
• Proximal muscle weakness
• Distal muscle weakness

SOURCES: OMIM MESH ORPHANET MENDELIAN

Tibial muscular dystrophy (TMD) is a distal myopathy characterized by weakness of the muscles of the anterior compartment of lower limbs, appearing in the fourth to seventh decade of life.

TIBIAL MUSCULAR DYSTROPHY Is also known as distal myopathy, udd type|tardive tibial muscular dystrophy|finnish tibial muscular dystrophy|tmd|udd myopathy|distal titinopathy

• Gait disturbance
• Cardiomyopathy
• Myopathy
• Respiratory failure
• Difficulty walking

SOURCES: ORPHANET OMIM MENDELIAN

Nemaline myopathy-2 is an autosomal recessive skeletal muscle disorder with a wide range of severity. The most common clinical presentation is early-onset (in infancy or childhood) muscle weakness predominantly affecting proximal limb muscles. Muscle biopsy shows accumulation of Z-disc and thin filament proteins into aggregates named 'nemaline bodies' or 'nemaline rods,' usually accompanied by disorganization of the muscle Z discs. The clinical and histologic spectrum of entities caused by variants in the NEB gene is a continuum, ranging in severity from the severe form with perinatal onset and fetal death to milder forms with later onset. The distribution of weakness can vary from generalized muscle weakness, more pronounced in proximal limb muscles, to distal-only involvement, although neck flexor weakness appears to be rather consistent. Histologic patterns range from a severe usually nondystrophic disturbance of the myofibrillar pattern to an almost normal pattern, with or without nemaline bodies, sometimes combined with cores (summary by Lehtokari et al., 2014).For a discussion of genetic heterogeneity of nemaline myopathy, see NEM3 (OMIM ).Mutations in the NEB gene are the most common cause of nemaline myopathy (Lehtokari et al., 2006).

• Generalized hypotonia
• Scoliosis
• Hypertelorism
• Muscle weakness
• Cleft palate

SOURCES: OMIM MESH MENDELIAN

Mosaic variegated aneuploidy is an autosomal recessive disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies but is usually more than 25% and is substantially greater than in normal individuals. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor, and leukemia reported in several cases (summary by Hanks et al., 2004). Genetic Heterogeneity of Mosaic Variegated Aneuploidy SyndromeSee also MVA2 (OMIM ), caused by mutation in the CEP57 gene (OMIM ) on chromosome 11q21, and MVA3 (OMIM ), caused by mutation in the TRIP13 gene (OMIM ) on chromosome 5p15.

MOSAIC VARIEGATED ANEUPLOIDY SYNDROME 1; MVA1 Is also known as mva syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM MENDELIAN

Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal anomaly characterized by multiple mosaic aneuploidies that leads to a variety of phenotypic abnormalities and cancer predisposition.

MOSAIC VARIEGATED ANEUPLOIDY SYNDROME Is also known as warburton-anyane-yeboa syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MENDELIAN

Autosomal recessive limb-girdle muscular dystrophy type 2R (LGMD2R) is a form of limb-girdle muscular dystrophy characterized by the adolescent or early adulthood-onset of progressive proximal muscle weakness and mild facial muscle weakness, with patients becoming wheelchair bound in their fourth to fifth decade of life. Mild, bilateral winged scapula, incomplete right bundle branch block, and a sinus rhythm with very rare ventricular extrasystoles have also been reported.

AUTOSOMAL RECESSIVE LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 2R Is also known as autosomal recessive limb-girdle muscular dystrophy due to desmin deficiency|lgmd2r

• Muscular dystrophy

SOURCES: ORPHANET 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

Autosomal recessive limb-girdle muscular dystrophy-1 affects primarily the proximal muscles, resulting in difficulty walking. The age at onset varies, but most patients show onset in childhood, and the disorder is progressive. Other features may include scapular winging, calf pseudohypertrophy, and contractures (summary by Mercuri et al., 2005). Genetic Heterogeneity of Autosomal Recessive Limb-Girdle Muscular DystrophyAutosomal recessive LGMD is genetically heterogeneous.LGMDR2 (OMIM ), previously symbolized LGMD2B, is caused by mutation in the dysferlin gene (DYSF ) on 2p13. LGMDR3 (OMIM ), previously symbolized LGMD2D, is caused by mutation in the alpha-sarcoglycan gene (SGCA ) on 17q21. LGMDR4 (OMIM ), previously symbolized LGMD2E, is caused by mutation in the beta-sarcoglycan gene (SGCB ) on 4q12. LGMDR5 (OMIM ), previously symbolized LGMD2C, is caused by mutation in the gamma-sarcoglycan gene (SGCG ) on 13q12. LGMDR6 (OMIM ), previously symbolized LGMD2F, is caused by mutation in the delta-sarcoglycan gene (SGCD ) on 5q33. LGMDR7 (OMIM ), previously symbolized LGMD2G, is caused by mutation in the TCAP gene (OMIM ) on 17q12. LGMDR8 (OMIM ), previously symbolized LGMD2H, is caused by mutation in the TRIM32 gene (OMIM ) on 9q33. LGMDR9 (OMIM ), previously symbolized LGMD2I, is caused by mutation in the FKRP gene (OMIM ) on 19q13. LGMDR10 (OMIM ), previously symbolized LGMD2J, is caused by mutation in the titin gene (TTN ) on 2q31. LGMDR11 (OMIM ), previously symbolized LGMD2K, is caused by mutation in the POMT1 gene (OMIM ) on 9q34. LGMDR12 (OMIM ), previously symbolized LGMD2L, is caused by mutation in the ANO5 gene (OMIM ) on 11p14. LGMDR13 (OMIM ), previously symbolized LGMD2M, is caused by mutation in the FKTN gene (OMIM ) on 9q31. LGMDR14 (OMIM ), previously symbolized LGMD2N, is caused by mutation in the POMT2 gene (OMIM ) on 14q24. LGMDR15 (OMIM ), previously symbolized LGMD2O, is caused by mutation in the POMGNT1 gene (OMIM ) on 1p34. LGMDR16 (OMIM ), previously symbolized LGMD2P, is caused by mutation in the DAG1 gene (OMIM ) on 3p21. LGMDR17 (OMIM ), previously symbolized LGMD2Q, is caused by mutation in the PLEC1 gene (OMIM ) on 8q24. LGMDR18 (OMIM ), previously symbolized LGMD2S, is caused by mutation in the TRAPPC11 gene (OMIM ) on 4q35. LGMDR19 (OMIM ), previously symbolized LGMD2T, is caused by mutation in the GMPPB gene (OMIM ) on 3p21. LGMDR20 (OMIM ), previously symbolized LGMD2U, is caused by mutation in the ISPD gene (OMIM ) on 7p21. LGMDR21 (OMIM ), previously symbolized LGMD2Z, is caused by mutation in the POGLUT1 gene (OMIM ) on 3q13.Some forms of autosomal recessive LGMD were reclassified by Straub et al. (2018). LGMD2R was reclassified as a form of myofibrillar myopathy (MFM1 ). For forms previously designated LGMD2W, LGMD2X, and LGMD2Y, see {616827}, {616812}, and {617072}, respectively.For a discussion of autosomal dominant LGMD, see LGMDD1 (OMIM ).

MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1; LGMDR1 Is also known as lgmd2|muscular dystrophy, limb-girdle, type 2a|lgmd2a|muscular dystrophy, pelvofemoral|calpainopathy|leyden-moebius muscular dystrophy|muscular dystrophy, limb-girdle, type 2

• Muscle weakness
• Flexion contracture
• Myopathy
• Elevated serum creatine phosphokinase
• Difficulty walking

SOURCES: OMIM MENDELIAN

Autosomal dominant limb-girdle muscular dystrophy type 1D (LGMD1D) is a subtype of autosomal dominant limb-girdle muscular dystrophy characterized by an adult-onset of slowly progressive, proximal pelvic girdle weakness, with none, or only minimal, shoulder girdle involvement, and absence of cardiac and respiratory symptoms. Mild to moderate elevated creatine kinase serum levels and gait abnormalities are frequently observed.

AUTOSOMAL DOMINANT LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 1D Is also known as lgmd1d|lgmd1e|muscular dystrophy, limb-girdle, type 1d, formerly|muscular dystrophy, limb-girdle, type 1e|lgmd1d, formerly

• Muscle weakness
• Flexion contracture
• Dysarthria
• Dysphagia
• Myopathy

SOURCES: OMIM ORPHANET MENDELIAN

Chronic granulomatous disease is a genetically heterogeneous immunodeficiency disorder resulting from an inability of phagocytes to kill microbes that they have ingested. This impairment in killing is caused by any of several defects in the phagocyte NADPH oxidase (phox) complex, which generates the microbicidal 'respiratory burst' (reviewed by Dinauer et al., 2001 and Johnston, 2001). Genetic Heterogeneity of Chronic Granulomatous DiseaseChronic granulomatous disease can be caused by mutations in any 1 of 5 genes encoding structural or regulatory subunits of the phagocyte NADPH oxidase complex. See also autosomal recessive cytochrome b-negative CGD (OMIM ), caused by mutation in the CYBA gene (OMIM ); autosomal recessive cytochrome b-positive CGD type I (OMIM ), caused by mutation in the NCF1 gene (OMIM ); autosomal recessive cytochrome b-positive CGD II (OMIM ), caused by mutation in the NCF2 gene (OMIM ); and autosomal recessive cytochrome b-positive CGD type III (OMIM ), caused by mutation in the NCF4 gene (OMIM ).A similar syndrome, termed neutrophil immunodeficiency syndrome (OMIM ), is caused by mutation in another protein involved in the NADPH oxidase complex, RAC2 (OMIM ).

GRANULOMATOUS DISEASE, CHRONIC, X-LINKED; CDGX Is also known as cytochrome b-negative granulomatous disease, chronic, x-linked|cgd|chronic granulomatous disease, x-linked

• Hepatomegaly
• Splenomegaly
• Immunodeficiency
• Recurrent infections
• Thrombocytopenia

SOURCES: OMIM MENDELIAN