ADA2 deficiency in a patient with Noonan syndrome‐like disorder with loose anagen hair: The co‐occurrence of two rare syndromes

Abstract

Noonan syndrome-like disorder with loose anagen hair (NS/LAH) is one of the RASopathies, a group of clinically related developmental disorders caused by germline mutations in genes that encode components acting in the RAS/MAPK pathway. Among RASopathies, NS/LAH (OMIM 607721) is an extremely rare, multiple anomaly syndrome characterized by dysmorphic facial features similar to those observed in Noonan syndrome along with some distinctive ectodermal findings including easily pluckable, sparse, thin, and slow-growing hair. ADA2 deficiency (DADA2, OMIM 615688) is a monogenic autoinflammatory disorder caused by homozygous or compound heterozygous mutations in ADA2, with clinical features including recurrent fever, livedo racemosa, hepatosplenomegaly, and strokes as well as immune dysregulation. This is the first report of NS/LAH and ADA2 deficiency in the same individual. We report on a patient presenting with facial features, recurrent infections and ectodermal findings in whom both the clinical and molecular diagnoses of NS/LAH and ADA2 deficiency were established, respectively. K E Y W O R D SADA2, consanguinity, DADA2, Noonan syndrome-like disorder with loose anagen hair, SHOC2

Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke

“…KFCG can regulate the activities of PKC (genes PRKCA, PRKCB, PRKCG), Ras (genes HRAS, KRAS, NRAS) (Ding M.-H. et al, 2020), Raf-1 (gene RAF1) (Ding M.-H. et al, 2020), phosphorylate SPK (genes SPHK1, SPHK2), and MEK (genes MAP2K1, MAP2K2) (Ding M.-H. et al, 2020), thereby affecting the arachidonic acid metabolism and cell proliferation through the MAPK signaling pathway. The reports have shown that Ras (Garavelli et al, 2015;Akgun-Dogan et al, 2019). Besides, KFCG can also phosphorylate IKK (genes CHUK, IKBKB, IKBKG) and regulate the activities of NFκB (genes NFKB1, NFKB2, RELA, RELB), thereby regulating cell Proliferation, inflammation, and anti-apoptosis.…”

A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review

“…Recurrent infections were described in 70 patients (18.5%) in terms of recurrent cutaneous infections as abscesses, widespread warts or molluscum contagiosum, severe gastrointestinal infections, respiratory infections, otitis, or opportunistic infections [ 1 , 4 , 7 – 9 , 12 , 17 , 19 , 21 , 22 , 30 – 33 , 38 , 39 , 42 , 44 , 45 , 49 , 58 , 59 , 61 , 63 , 64 , 71 , 77 , 82 , 83 , 87 , 88 ].…”

“…The abdominal involvement was described in terms of recurrent abdominal pain, recurrent diarrhoea, gastrointestinal bleeding, intestinal ischaemia, bowel perforation, increased transaminase [ 1 , 2 , 4 , 5 , 8 , 11 , 12 , 16 , 19 , 20 , 22 – 25 , 28 , 30 – 32 , 36 , 37 , 40 , 43 , 45 , 47 , 52 , 56 , 57 , 59 , 63 – 66 , 69 , 72 , 74 , 76 – 78 , 80 , 82 , 87 ].…”

The Many Faces of a Monogenic Autoinflammatory Disease: Adenosine Deaminase 2 Deficiency

“…Both FMF and DADA2 are known to have increased allele frequency in the Turkish population, possibly explaining their co-occurrence in this population. Noonan Syndrome-like disorder with loose anagen hair [70] and X-linked recessive nephrolithiasis (i.e., Dent's disease) [71] have been described. Two siblings with chronic mucocutaneous candidiasis, retinal vasculitis, elevated IgG, and neutropenia were found to have a 770-kb deletion on chromosome 22q11.1 encompassing both the IL17 receptor gene and ADA2 [33] (Table 1).…”

“…ADA2 was purified in 2005 and determined to be encoded by the ADA2 gene (formally CECR1), located on chromosome 22q11.1 [ 6 ••, 23 ]. A variety of types of mutations have since been reported including missense, nonsense, splice site mutations, frameshift mutations, deletions, and copy number variations [ 16 , 61 , 70 ]. Between 2014 and 2020, at least an additional 67 known pathogenic mutations were documented, with a total of 98 known variants, many not classified, of uncertain significance, or potentially benign [ 72 ••].…”