TY - JOUR
T1 - Biallelic variants of the first Kunitz domain of SPINT2 cause a non-syndromic form of congenital diarrhea and tufting enteropathy
AU - Al Rawahi, Yusriya
AU - Al Sunaidi, Omar
AU - Al-Masqari, Mohammed
AU - Al Jamei, Adawiya
AU - Rahamtalla, Dafalla
AU - Al-Maawali, Almundher
N1 - Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2023/11/13
Y1 - 2023/11/13
N2 - Biallelic SPINT2 pathogenic variants cause a syndromic form of congenital diarrhea and enteropathy (OMIM 270420). To date, 35 patients have been reported and all presented with additional extra-intestinal features, apart from one case. We report on a 5-year-old girl who presented early in life with diarrhea and was found to have a novel homozygous variant in SPINT2. Pathological studies confirmed tufting enteropathy, and during her 5 years of life, she has not developed any extra-intestinal features. Molecular analysis detected a homozygous variant (NM_021102.4: c.203A>G (p. [Tyr68Cys]) in SPINT2. This is the first missense variant reported in the first Kunitz domain (KD1) of SPINT2 in humans. In vitro functional studies of this variant confirmed the deleterious effect leading to the loss of inhibitory activity of the intestinal serine proteases. This is the first description of SPINT2-related diarrhea in a patient who lived without long-term total parenteral nutrition. This study expands the clinical and molecular characteristics of SPINT2-related conditions.
AB - Biallelic SPINT2 pathogenic variants cause a syndromic form of congenital diarrhea and enteropathy (OMIM 270420). To date, 35 patients have been reported and all presented with additional extra-intestinal features, apart from one case. We report on a 5-year-old girl who presented early in life with diarrhea and was found to have a novel homozygous variant in SPINT2. Pathological studies confirmed tufting enteropathy, and during her 5 years of life, she has not developed any extra-intestinal features. Molecular analysis detected a homozygous variant (NM_021102.4: c.203A>G (p. [Tyr68Cys]) in SPINT2. This is the first missense variant reported in the first Kunitz domain (KD1) of SPINT2 in humans. In vitro functional studies of this variant confirmed the deleterious effect leading to the loss of inhibitory activity of the intestinal serine proteases. This is the first description of SPINT2-related diarrhea in a patient who lived without long-term total parenteral nutrition. This study expands the clinical and molecular characteristics of SPINT2-related conditions.
KW - SPINT2
KW - congenital diarrhea
KW - total parenteral nutrition
KW - tufting enteropathy
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UR - https://www.mendeley.com/catalogue/fb09d9e9-670c-3309-b03c-47eab32cde1f/
U2 - 10.1002/ajmg.a.63474
DO - 10.1002/ajmg.a.63474
M3 - Article
C2 - 37960980
AN - SCOPUS:85176914138
SN - 1552-4825
VL - 194
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 3
M1 - e63474
ER -