ClinVar Genomic variation as it relates to human health

Lymphopenia (present) , Decreased helper T cell proportion (present) , Vitiligo (present) , Recurrent Haemophilus influenzae infections (present) , Arthralgia (present) , Onychomycosis (present) , Chronic oral candidiasis (present) , Chronic mucocutaneous candidiasis (present) (less)

In studies of 16 North American cases of autoimmune polyendocrinopathy syndrome type I (APS1; 240300), Heino et al. (1999) found that a 1094-1106del mutation accounted for 17 of 32 alleles. The deletion of 13 nucleotides accounted for 5 of 18 northern Italian alleles (Finnish-German APECED Consortium, 1997). This mutation is the same as that designated 964del13 by Pearce et al. (1998) and 967-979del13 by Heino et al. (2001). In 9 of 16 patients with APS1, Wang et al. (1998) found a 13-bp deletion (1094-1106del) in exon 8 of the AIRE gene; 7 were homozygotes and 2 compound heterozygotes. Nithiyananthan et al. (2000) stated that the 13-bp deletion at nucleotide 964 in exon 8 (964del13) of the AIRE gene on chromosome 21q22.3 accounts for more than 70% of mutant alleles in United Kingdom subjects with APECED. The authors concluded that this mutation is not a susceptibility locus for the more common autoimmune endocrinopathies in the United Kingdom. In a patient diagnosed by Brodehl et al. (1967) with isolated hypercystinuria (see 220100) who was subsequently found to have autoimmune polyendocrinopathy type I, Eggermann et al. (2007) identified compound heterozygosity for the common mutations R257X (607358.0001) and 964del13. Two older sibs had died from hypocalcemic tetany. Wolff et al. (2007) found that this mutation was the most prevalent in Norwegian patients with APS1; it was present in 23 of 48 alleles. Harris et al. (2003) described 2 unrelated children with, in addition to APECED, a progressive skeletal deformity that spontaneously resolved in the mid-teen years. Both children carried the 964del13 mutation, one in homozygosity and the other in compound heterozygosity with a 1-bp deletion (607358.0009). In 4 patients with APS1 from 3 Indian families from unrelated caste groups, Zaidi et al. (2009) identified homozygosity for the 13-bp deletion, which they called 967_979del13. The parents were all heterozygous for the mutation. One patient, a 4-year-old girl who presented at age 2 years with type 1 diabetes mellitus (222100), died of septicemia. In 3 sibs with hypoparathyroidism, including a sister who had premature ovarian failure, Li et al. (2017) identified compound heterozygous mutation in the AIRE gene: the recurrent 13-bp deletion (607358.0003) and a splicing mutation (c.995+(3_5)delGAGinsTAT; 607358.0012). Their unaffected parents were each heterozygous for 1 of the mutations, and unaffected offspring were either heterozygous or wildtype. Noting that the patients were in the sixth and seventh decades of life, and that multiple manifestations of APS1 would normally have developed by the fifth decade of life, the authors stated that it was unclear why 2 of the 3 patients had such a limited APS1 phenotype. However, the near-constant development of hypoparathyroidism in APS1 suggested that parathyroid involvement occurs at a very low threshold and represents a very mild expression of the disease. In 2 unrelated children, aged 11 and 16 years, who exhibited apparent isolated hypoparathyroidism, Cranston et al. (2022) identified homozygosity for the 13-bp deletion in the AIRE gene. The authors noted that autoimmune parathyroid gland destruction represents an early manifestation of APS1, with a peak incidence at around 5 years of age, and suggested that the probands might well develop additional features of APS1. (less)

In studies of 16 North American cases of autoimmune polyendocrinopathy syndrome type I (APS1; 240300), Heino et al. (1999) found that a 1094-1106del mutation accounted for 17 of 32 alleles. The deletion of 13 nucleotides accounted for 5 of 18 northern Italian alleles (Finnish-German APECED Consortium, 1997). This mutation is the same as that designated 964del13 by Pearce et al. (1998) and 967-979del13 by Heino et al. (2001). In 9 of 16 patients with APS1, Wang et al. (1998) found a 13-bp deletion (1094-1106del) in exon 8 of the AIRE gene; 7 were homozygotes and 2 compound heterozygotes. Nithiyananthan et al. (2000) stated that the 13-bp deletion at nucleotide 964 in exon 8 (964del13) of the AIRE gene on chromosome 21q22.3 accounts for more than 70% of mutant alleles in United Kingdom subjects with APECED. The authors concluded that this mutation is not a susceptibility locus for the more common autoimmune endocrinopathies in the United Kingdom. In a patient diagnosed by Brodehl et al. (1967) with isolated hypercystinuria (see 220100) who was subsequently found to have autoimmune polyendocrinopathy type I, Eggermann et al. (2007) identified compound heterozygosity for the common mutations R257X (607358.0001) and 964del13. Two older sibs had died from hypocalcemic tetany. Wolff et al. (2007) found that this mutation was the most prevalent in Norwegian patients with APS1; it was present in 23 of 48 alleles. Harris et al. (2003) described 2 unrelated children with, in addition to APECED, a progressive skeletal deformity that spontaneously resolved in the mid-teen years. Both children carried the 964del13 mutation, one in homozygosity and the other in compound heterozygosity with a 1-bp deletion (607358.0009). In 4 patients with APS1 from 3 Indian families from unrelated caste groups, Zaidi et al. (2009) identified homozygosity for the 13-bp deletion, which they called 967_979del13. The parents were all heterozygous for the mutation. One patient, a 4-year-old girl who presented at age 2 years with type 1 diabetes mellitus (222100), died of septicemia. In 3 sibs with hypoparathyroidism, including a sister who had premature ovarian failure, Li et al. (2017) identified compound heterozygous mutation in the AIRE gene: the recurrent 13-bp deletion (607358.0003) and a splicing mutation (c.995+(3_5)delGAGinsTAT; 607358.0012). Their unaffected parents were each heterozygous for 1 of the mutations, and unaffected offspring were either heterozygous or wildtype. Noting that the patients were in the sixth and seventh decades of life, and that multiple manifestations of APS1 would normally have developed by the fifth decade of life, the authors stated that it was unclear why 2 of the 3 patients had such a limited APS1 phenotype. However, the near-constant development of hypoparathyroidism in APS1 suggested that parathyroid involvement occurs at a very low threshold and represents a very mild expression of the disease. In 2 unrelated children, aged 11 and 16 years, who exhibited apparent isolated hypoparathyroidism, Cranston et al. (2022) identified homozygosity for the 13-bp deletion in the AIRE gene. The authors noted that autoimmune parathyroid gland destruction represents an early manifestation of APS1, with a peak incidence at around 5 years of age, and suggested that the probands might well develop additional features of APS1. (less)

Lymphadenopathy (present) , Abnormality of the immune system (present) , Mastocytosis (present) , Recurrent infections (present) , Epistaxis (present) , Gastroesophageal reflux (present) , Rhinitis (present) , Tachycardia (present) , Dry skin (present) , Chest tightness (present) , Fatigue (present) , Cardiac arrhythmia (present) , Edema (present) , Inflammatory abnormality of the skin (present) , Allergic rhinitis (present) , Xerostomia (present) , Arthralgia (present) , Immunodeficiency (present) , Cough (present) , Dyspnea (present) , Orthostatic tachycardia (present) , Headache (present) , Fever (present) , Asthma (present) , Sepsis (present) , Nausea (present) , Allergy (present) , Vomiting (present) , Skin ulcer (present) , Facial erythema (present) , Urticaria (present) , Chronic oral candidiasis (present) , Vocal cord dysfunction (present) , Pruritus (present) , Skin rash (present) (less)